Assisted manual injector devices and methods

ABSTRACT

Various embodiments disclosed herein relate to needle-based injectors that incorporate a power assembly comprising a stored energy source and a rate control assembly. The power assembly may be further configured to allow the injection to be performed with more force than a user may be capable of delivering, while also allowing the user to maintain control of the injection process after the stored energy source has been released and the injection has begun, such the user may increase or decrease the rate of injection, or stop the injection, during the injection process. In various embodiments, the power assembly may comprise spring- or gas-based stored energy sources, and/or may comprise friction- or tension-based rate control assemblies. Described herein are also methods for injecting an agent using embodiments of the devices described here.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority benefit of U.S. ProvisionalApplication Ser. No. 61/903,884, filed Nov. 13, 2013, which isincorporated herein by reference in its entirety.

FIELD

Described here are power-assisted injection devices that allow a user toselectively increase or decrease the injection rate, and to pause orstop the injection, as desired.

BACKGROUND

The injection of therapeutic agents in hospital, clinic, and home-basedsettings is a common procedure, but can sometimes be complex anddifficult to perform, even for experienced healthcare providers. Drawinga therapeutic agent into a syringe and injecting it into a patientrequires a certain level of manual dexterity and strength, in additionto sufficient visual and mental acuity to perform the procedural steps.The risk of needlestick injury also exists throughout all of the stepsof a manual injection procedure. In home-based settings, thesechallenges could lead to reduced patient compliance with treatmentregimens.

Nevertheless, as reliance upon home-based injection regimens continuesto expand, the challenges with syringe injection have become morediversified. For example, patients with physical or cognitive impairmentmay need to perform such injections, without assistance from in-homecare providers. Also, some injections require more force than users arecapable of delivering, for instance if the injected substance has a highviscosity. Furthermore, for some medications, the injection process cancause discomfort related to the rate of injection. In some instances, auser may want to increase the rate of injection, in order to accomplishthe injection in a shorter time, or may want to decrease the rate ofinjection or stop the injection, for example to mitigateinjection-related pain. There is therefore a need for a power-assistedinjection device, which allows the user to both control a stored energysource and also provide some amount of user supplied power to theinjection, and thus increase or decrease the injection rate, or stop theinjection, at will.

BRIEF SUMMARY

Various embodiments disclosed herein relate to needle-based injectorsthat incorporate a power assembly comprising a stored energy source anda rate control assembly. The power assembly may be further configured toallow the injection to be performed with more force than a user may becapable of delivering, while also allowing the user to maintain controlof the injection process after the stored energy source has beenreleased and the injection has begun, such the user may increase ordecrease the rate of injection, or stop the injection, during theinjection process. In various embodiments, the power assembly maycomprise spring- or gas-based stored energy sources, and may comprisefriction- or tension-based rate control assemblies. Described herein arealso methods for injecting an agent using embodiments of the devicesdescribed here.

A particular embodiment comprises a device for injecting an agent,comprising a syringe comprising a syringe cavity, a plunger elementslidably received in the syringe cavity, and a hollow needle in fluidcommunication with the syringe cavity, wherein the plunger element isconfigured to move from a proximal position to a distal position, apower assembly configured to transmit force to the plunger element, anda user-actuated brake assembly that is configured to reversibly resistmovement of the plunger element in at least one intermediate positionbetween the proximal position and the distal position. The brakeassembly may be biased to resist movement of the plunger element when inan inactivated state, and may permit movement of the plunger elementwhen in an activated state. The brake assembly may be biased by a brakespring to resist movement of the plunger element. The power assembly maycomprise a mechanical spring. The plunger element may be furtherconfigured to simultaneously receive user-applied force that moves theplunger element toward the distal position. The device may furthercomprise a housing wherein the syringe is located in the housing. Thehousing may be coupled to the plunger element. The housing may beconfigured to transmit user-applied force to the plunger element. Thebrake assembly may comprise a flexible, elongate brake cord. The brakecord may comprise a releasable friction fit to reversibly resistmovement of the plunger element. The releasable friction fit may beprovided by releasable tension in the brake cord. The brake assembly maycomprise a rigid friction element. The brake assembly may act on anouter surface of the syringe to reversibly resist movement of theplunger element. The brake assembly may act on a surface fixed relativeto the syringe to reversibly resist movement of the plunger element. Thebrake assembly may comprise an opening in which the syringe resides. Thepower assembly may be configured to pull the plunger element toward thedistal position. The power assembly may be configured to push theplunger element toward the distal position. The power assembly may befurther configured to push and pull the plunger element toward thedistal position. The syringe may be slidably located in the housing andthe syringe is configured to move from a retracted position where adistal tip of the needle lies within the housing, toward an extendedposition where the distal tip of the needle extends distal to thehousing. The device may further comprise an extendable needle shroud,wherein the needle shroud may be configured with a releasably locked,retracted state relative to the syringe, and an unlocked state that maypermit movement toward an extended position relative to the syringe. Thedevice may further comprise an extendable needle shroud, wherein theneedle shroud is configured with a releasably locked, retracted staterelative to the syringe, and an unlocked state that permits movementtoward an extended position relative to the syringe, and wherein theneedle shroud is further configured to change to the unlocked statebefore the distal tip of the needle extends distal to the housing. Theneedle shroud may be further configured to relock when the needle shroudreaches the extended state. In other variations the device may comprisean extendable needle shroud, wherein the needle shroud is configuredwith an unlocked extended state that permits movement toward a retractedposition relative to the syringe and a locked extended state. The needleshroud may be configured to enter the locked extended state when theneedle shroud extends from a retracted state.

A particular embodiment comprises a device for injecting an agent,comprising a syringe comprising a syringe cavity containing aformulation comprising the agent, and a power assembly configured to actupon the syringe to cause the formulation to be displaced from thesyringe cavity, wherein the power assembly comprises a stored energysource and a rate control assembly, wherein the rate control assemblyresists the stored energy source acting on the syringe when in a firstconfiguration and allows the stored energy source to act on the syringewhen in a second configuration. The rate control assembly may partiallyresist the stored energy source acting on the syringe in a thirdconfiguration. The device may further comprise a housing, wherein thesyringe and power assembly are at least partially located within thehousing. The rate control assembly may be configured to be changed fromthe first configuration to the second configuration by application ofdistal force on the housing. The change from the first configuration tothe second configuration may be reversible. The rate control assemblymay be configured to be changed from the second configuration to thefirst configuration by removing or reducing the application of distalforce on the housing. The change from the second configuration to thefirst configuration may be reversible. The housing may comprise aproximal housing and a distal housing, and wherein the application ofdistal force on the housing may be to the proximal housing. The distalhousing may comprise a distal end and a nose located at the distal end,and wherein the nose has a flared shape. The syringe may furthercomprise a plunger slidable within the syringe cavity and a needlehaving a lumen in fluid communication with the syringe cavity, whereinthe syringe may be configured such that distal movement of the plungerwithin the syringe cavity may cause the formulation to be displaced fromthe syringe cavity through the lumen of the needle. In the firstconfiguration, the rate control assembly may resist distal movement ofthe plunger within the syringe cavity. In the second configuration, therate control assembly may allow distal movement of the plunger withinthe syringe cavity. The stored energy source may comprise a spring. Therate control assembly may comprise a longitudinal axis and the housingmay comprise a longitudinal axis, and the rate control assembly may beconfigured to be reversibly moved from the first configuration to thesecond configuration by moving the longitudinal axis of the rate controlassembly toward the longitudinal axis of the housing. The stored energysource may comprise a composite spring, wherein the composite spring maycomprise a coaxially arranged compression spring and extension spring.The rate control assembly may comprise a cord comprising at least twoportions capable of being under differing amounts of tension. The storedenergy source may comprise a compressed gas or liquid propellant in asupercritical state. The device is configured such that the rate atwhich the formulation is able to be displaced from the syringe cavitymay be able to be selectively increased, decreased, or stopped after theplunger has moved distally relative to an initial position within thesyringe cavity. The device may be configured such that movement of theplunger distally within the syringe cavity may require application ofdistal force by a user during the movement.

A particular embodiment comprises a device for injecting an agent,comprising a syringe comprising a syringe cavity containing aformulation comprising the agent to be injected by application of distalforce on the device by a user, and a power assembly configured to actupon the syringe, wherein the power assembly is configured to amplifythe application of distal force by the user, such that the agent is ableto be injected with more distal force than is applied by the user to thedevice, and wherein the power assembly is configured to reduce the rateof injection of the agent if the distal force is reduced. The powerassembly may be configured to stop the injection of the agent if theuser stops applying distal force to the device. The formulation may be aliquid formulation. The formulation may be a colloidal formulation.

A particular embodiment comprises a device for injecting an agent,comprising a syringe comprising a syringe cavity, a plunger elementslidably received in the syringe cavity, and a hollow needle in fluidcommunication with the syringe cavity, wherein the plunger is configuredto move from a proximal position to a distal position, a pressurized gasassembly with a user-actuated valve opening biased to a closed state,and a flow path between the valve opening and a pressurization region,wherein the flow path is non-linear. The pressurized gas assembly may beconfigured to apply force to a surface at a fixed position relative tothe plunger to move the plunger from the proximal position to the distalposition. The plunger may be further configured to simultaneouslyreceive user-applied force that moves the plunger element toward thedistal position. The device may further comprise a housing wherein thesyringe may be at least partially located in the housing. The housingmay be configured to transmit user-applied force to the plunger. Thehousing may be configured to transmit user-applied force to the valveopening. The valve opening may be configured to be opened byuser-applied force to the housing. The syringe may be slidably locatedin the housing and the syringe may be configured to move from aretracted position where a distal tip of the needle lies within thehousing, toward an extended position where the distal tip of the needleextends distal to the housing. The device may further comprise anextendable needle shroud, wherein the needle shroud may be configuredwith a releasably locked, retracted state relative to the syringe, andan unlocked state that may permit movement toward an extended positionrelative to the syringe. The device may further comprise an extendableneedle shroud, wherein the needle shroud may be configured with areleasably locked, retracted state relative to the syringe, and anunlocked state that may permit movement toward an extended positionrelative to the syringe, and wherein the needle shroud maybe furtherconfigured to change to the unlocked state before the distal tip of theneedle extends distal to the housing. The needle shroud may be furtherconfigured to relock when the needle shroud reaches the extended state.The pressurization region may be configured to have a variable volume.

A particular embodiment comprises a device for injecting an agent,comprising a housing, and a syringe located within the housing, whereinthe housing comprises a needle shroud having activated and inactivatedconfigurations, wherein when the needle shroud is in an activatedconfiguration, it is biased from a retracted position toward an extendedposition, and wherein the needle shroud is switched from the inactivatedconfiguration to the activated configuration by distal motion of thesyringe relative to at least a portion of the housing. The syringe maycomprise a needle and the syringe may be slidably located in the housingand may be configured to move from a retracted position where a distaltip of the needle lies within the housing, toward an extended positionwhere the distal tip of the needle extends distal to the housing. Theneedle shroud may be switched from the inactivated configuration to theactivated configuration before the distal tip of the needle extendsdistal to the housing. The needle shroud may be configured to bemaintained in a retracted position by proximal force on the needleshroud after being switched to an activated configuration. The needleshroud may be further configured to be locked in an extended positiononce moved to an extended position.

A particular embodiment comprises a device for injecting an agent,comprising a housing having a longitudinal axis, a syringe containingthe agent located within the housing, a plunger slidable within thesyringe, configured to be moveable between a proximal position and adistal position, wherein moving the plunger toward the distal positiondisplaces the agent from the syringe, a biter having a longitudinal axisand comprising a lumen through which the syringe is located, wherein thebiter is configured to be moveable between a first configuration whereinthe longitudinal axis of the biter is offset from the longitudinal axisof the housing, and a second configuration wherein the longitudinal axisof the biter is less offset from the longitudinal axis of the housingthan in the first configuration, and a spring in contact with the biterconfigured to bias the plunger toward the distal position via the biterwhen the biter is in the second configuration. The spring may bias thebiter toward the first configuration. The syringe may be configured tobe moveable between a proximal position and a distal position relativeto the housing. The biter may be configured to be moveable between thefirst configuration and the second configuration by moving an actuationrod between a first position not in contact with the biter and a secondposition in contact with the biter. The biter may configured to bemoveable between the first configuration and the second configuration byapplication of distal force on the housing. The spring may apply adistal force on the biter. The distal force on the biter from the springmay be opposed by a proximal frictional force when the biter is in thefirst configuration. The device may further comprise a retractableneedle shroud configured to be moveable between a retracted position andan extended position. The device may further comprise an end-of-doseindicator moveable between an inactivated and an activatedconfiguration.

A particular embodiment may comprise a device for injecting an agent,comprising a housing, a syringe located within the housing, wherein thesyringe comprises the agent, a plunger configured to move slidablywithin the syringe between a proximal and a distal position, a springconfigured to bias the plunger toward the distal position, and a cordconfigured to be reversibly changed between a tensioned configurationand an reduced-tension configuration, wherein the cord is configured tobias the plunger toward the proximal position when in the tensionedconfiguration. The plunger may be configured to remain fixed relative tothe syringe when the cord is in a tensioned configuration. The plungermay be configured to move toward the distal position when the cord is ina reduced-tension configuration. The plunger may comprise a distal end,and the cord may be configured to apply proximal force to the distal endof the plunger when the cord is in the tensioned configuration. Thespring may be configured to pull the plunger toward the distal position.

A particular embodiment may comprise a device for injecting an agent,comprising a housing, a syringe located within the housing, and anend-of-dose indicator, wherein the end-of-dose indicator has aninactivated configuration and an activated configuration, and whereinthe visual appearance of the end-of-dose indicator through the housingis different in the inactivated and activated configurations. Thesyringe may further comprise a syringe cavity and a plunger slidablyreceived in the syringe cavity, and a hollow needle in fluidcommunication with the syringe cavity, wherein the plunger may beconfigured to move from a proximal position to a distal position, andwherein the end-of-dose indicator is moved from the inactivatedconfiguration to the activated configuration by movement of the plungertoward the distal position.

A particular embodiment may comprise a method for injecting an agentusing a device comprising a syringe comprising a syringe cavity, ahousing wherein the syringe is located in the housing, a plungerslidably received in the syringe cavity, and a hollow needle in fluidcommunication with the syringe cavity, wherein the plunger is configuredto move from a proximal position to a distal position, a power assemblyconfigured to transmit force to the plunger, and a user-actuated brakeassembly that is configured to reversibly resist movement of the plungerin at least one intermediate position between the proximal position andthe distal position, comprising applying force to the housing, whereinthe force causes the power assembly to transmit force to the plunger tomove the plunger toward the distal position, and reducing the appliedforce to the housing when the plunger is in an intermediate position,wherein reducing the applied force causes the brake assembly to reducethe force transmitted to the plunger by the power assembly. The housingmay comprise a proximal housing and a distal housing, and whereinapplying force to the housing comprises applying distal force to theproximal housing. The force applied to the housing may further cause thebrake assembly to move from an inactivated state to an activated state,wherein the brake assembly may be biased to resist movement of theplunger element when in the inactivated state, and may permit movementof the plunger element when in the activated state. The method mayfurther comprise reapplying force to the housing, wherein the force maycause the power assembly to transmit force to the plunger to move theplunger toward the distal position.

A particular embodiment comprises a device for injecting an agent,comprising a housing having a longitudinal axis, a syringe containingthe agent within a syringe cavity, wherein the syringe is located withinthe housing, a plunger slidable within the syringe, configured to bemoveable between a proximal position and a distal position, whereinmoving the plunger toward the distal position displaces the agent fromthe syringe, and a spring in contact with the plunger configured to biasthe plunger toward the distal position, wherein the plunger comprises abraking pad configured to be reversibly moveable between a firstconfiguration and a second configuration, wherein the braking padgenerates friction to resist movement of the plunger in the secondconfiguration. The braking pad may be configured to be moveable from thefirst configuration to the second configuration by radially outwardmovement. The device may further comprise a stopper located within theplunger and movable between a proximal position and a distal positionwithin the plunger, wherein the stopper is configured such that movingthe stopper from the distal position to the proximal position moves thebraking pad from the first configuration to the second configuration.The stopper may be biased toward the proximal position. The stopper maybe configured to be moveable between the proximal position and distalposition by application of distal force on the housing. The device mayfurther comprise a retractable needle shroud configured to be moveablebetween a retracted position and an extended position. The device mayfurther comprise an end-of-dose indicator moveable between aninactivated and an activated configuration.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a perspective view of one embodiment of an injectiondevice.

FIGS. 2A-2N are longitudinal cross-sectional views the embodiment of aninjection device of FIG. 1 in various stages during use. FIGS. 2A-2Bshow two orthogonal cross-sectional views of the device before use.FIGS. 2C-2D show two orthogonal cross-sectional views of the device withthe rigid needle shield and cap removed. FIGS. 2E-2F show two orthogonalcross-sectional views of the device with the syringe partially movedtoward an extended position. FIGS. 2G-2H show two orthogonalcross-sectional views of the device with the syringe in an extendedposition. FIGS. 2I-2J show two orthogonal cross-sectional views of thedevice with the plunger partially moved toward a distal position withinthe syringe cavity. FIGS. 2K-2L two orthogonal cross-sectional views ofthe device with the plunger moved to the distal position within thesyringe cavity. FIGS. 2M-2N show two orthogonal cross-sectional views ofthe device with the needle shroud extended.

FIGS. 3A-3F are longitudinal cross-sectional views of a distal portionof the injection device of FIG. 1, showing the needle shroud in aretracted position (FIGS. 3A-3B), unlocked from a retracted position(FIGS. 3C-3D), and in an extended position (FIGS. 3E-3F).

FIGS. 4A-4C illustrate longitudinal cross-sectional views of a proximalportion of the injection device of FIG. 1, showing the end-of-doseindicator in inactivated (FIG. 4A), released (FIG. 4B), and activatedconfigurations (FIG. 4C). FIGS. 4D-4E illustrate cut-away elevationalside views of a proximal portion of another embodiment of an injectiondevice showing another example of an end-of-dose indicator ininactivated (FIG. 4D) and activated configurations (FIG. 4E).

FIG. 5 depicts an exploded perspective view of the injection device 100.

FIGS. 6A-6B are orthogonal longitudinal cross-sectional views of acentral portion of the injection device of FIG. 1, showing theinterlocker.

FIG. 7 depicts a perspective view of the stored energy source of theinjection device of FIG. 1.

FIGS. 8A-8B are perspective side views of the rate control assembly ofthe injection device of FIG. 1.

FIG. 9 illustrates a longitudinal cross-sectional view of the ratecontrol assembly.

FIG. 10 is a perspective view of another embodiment of an injectiondevice.

FIGS. 11A-11B are elevational side views of the injection device of FIG.10 with the cap attached and removed, respectively.

FIGS. 12A-12F are longitudinal cross-sectional views the embodiment ofan injection device of FIG. 10 in various stages during use. FIG. 12Adepicts the device before use. FIG. 12B depicts the device with therigid needle shield and cap removed. FIG. 12C depicts the device withthe syringe in an extended position. FIG. 12D depicts the device withthe plunger moved to the distal position within the syringe cavity. FIG.12E depicts the device with the end-of-dose indicator in an activatedconfiguration. FIG. 12F depicts the device with the needle shroudextended.

FIGS. 13A-13D depict longitudinal cross-sectional views (FIGS. 13A and13C) and cut-away elevational side views (FIGS. 13B and 13D) of a distalportion of the injection device of FIG. 10, showing the needle shroud ina retracted position and in an extended position, respectively.

FIGS. 14A-14B are longitudinal cross-sectional views and cut-awayelevational side views, respectively, of a proximal portion of theinjection device of FIG. 10, showing the end-of-dose indicator in anactivated configuration.

FIG. 15 illustrates a perspective view of the syringe and syringe sleeveof the injection device of FIG. 10.

FIGS. 16A-16B depict cut-away side elevational and longitudinalcross-sectional views, respectively, of the ram and power assembly ofthe injection device of FIG. 10. FIGS. 16C-16D shows perspective viewsof the base retainer cap and ram interlock, respectively.

FIG. 17 is a perspective view of the power assembly of the injectiondevice of FIG. 10.

FIG. 18 is a perspective view of another embodiment of an injectiondevice.

FIGS. 19A-19G illustrate longitudinal cross-sectional views of theembodiment of an injection device of FIG. 17 in various stages duringuse. FIG. 19A illustrates the device before use. FIG. 19B illustratesthe device with the rigid needle shield and cap removed. FIG. 19Cillustrates the device with the syringe in a partially extendedposition. FIG. 19D illustrates the device with the syringe in a fullyextended position. FIG. 19E illustrates the device with the plungermoved partially toward the distal position within the syringe cavity.FIG. 19F illustrates the device with the plunger in the distal positionwithin the syringe cavity. FIG. 19G illustrates the device with theneedle shroud extended.

FIG. 20A depicts a longitudinal cross-sectional view of the pressurepathway of the injection device of FIG. 18, with arrow indicating thepathway. FIG. 20B shows a closer view of a portion of the pressurepathway of FIG. 20A. FIG. 20C depicts a longitudinal cross-sectionalview of the venting pathway of the injection device of FIG. 18.

FIG. 21 shows an illustrative graph of the user force required toperform an injection using an injection device similar to the injectiondevice of FIG. 1.

FIG. 22 shows an illustrative graph of the user force required toperform an injection using an injection device similar to the injectiondevice of FIG. 10.

FIG. 23 shows a graph of an illustrative load multiplication factor foran injection device similar to the injection device of FIG. 18.

FIG. 24A shows a schematic representation of a model of atwo-dimensional friction-based biter having two contact points. FIG. 24Bshows a schematic representation of a model of a friction-based biterhaving three contact points.

FIGS. 25A-25C show schematic representations of configurations of theproximal and distal housing of injection devices.

FIG. 26 is a perspective view of another embodiment of an injectiondevice.

FIGS. 27A-27H illustrate longitudinal cross-sectional views of theembodiment of an injection device of FIG. 26 in various stages duringuse. FIG. 27A illustrates the device before use. FIG. 27B illustratesthe device with the syringe in a partially extended position. FIG. 27Cillustrates the device with the syringe in a fully extended position.FIG. 27D illustrates the device with the ram in contact with the seal.FIG. 27E illustrates the device with the plunger moved partially towardthe distal position within the syringe cavity. FIG. 27F illustrates thedevice with the end-of-dose indicator in an activated configuration.FIG. 27G illustrates the device with the plunger in the distal positionwithin the syringe cavity. FIG. 27H illustrates the device with theneedle shroud extended.

FIGS. 28A, 28B, and 28C show a distal portion of the injection device ofFIG. 26 with the needle safety assembly in initial extended, retracted,and locked extended configurations, respectively.

FIGS. 29A, 29B, and 29C depict perspective views of the needle safetyassembly, interlock ring, and shroud locking ring, respectively, of theinjection device of FIG. 26.

FIG. 30 depicts a perspective view of the ram of the injection device ofFIG. 26.

FIG. 31 shows an illustrative graph of the user force required toperform an injection using an injection device similar to the injectiondevice of FIG. 26.

DETAILED DESCRIPTION

Generally, the injection devices described herein may comprise ahousing, which may contain a syringe and a power assembly. In general,the housing may comprise a proximal housing and a distal housing. Theproximal and distal housings may be configured to fit slidably togetherto form a cavity of variable size. The syringe and power assembly may belocated within the cavity formed by the proximal and distal housings,and force applied to the housing may be translated into force on thesyringe and/or power assembly to cause an injection to proceed. In somevariations, the housing may comprise certain safety features, such as aretractable needle safety assembly, to limit accidental needlesticks,and/or indicators to indicate the progress or completion of theinjection.

The syringe may reside within the housing and may comprise a syringebody defining a syringe cavity, and a seal slidably disposed within thesyringe cavity defining a reservoir that may hold a formulationcomprising a therapeutic or diagnostic agent, a ram comprising a plungerthat may fit slidably within the syringe cavity, and a needle at thedistal end of the syringe body. The needle may be configured to piercethe tissue of a patient receiving an injection, and may have a lumentherethrough to deliver the contents of the reservoir to the patient'stissue. Movement of the seal within the syringe cavity distally maycause the contents of the reservoir to be displaced through the lumen ofthe needle.

The power assembly may comprise a stored energy source and a ratecontrol assembly. The stored energy source, when released, may beconfigured to transmit force to displace the contents of reservoir ofthe syringe through the lumen of the needle and into the patient. Insome variations, the user's input force onto the device may work inconjunction with the stored energy source to also provide force todisplace the reservoir contents. In some further variations, the storedenergy source may be configured to do so by contributing to the distalmotion of the plunger or seal within the syringe cavity. The ratecontrol assembly may limit or restrict the stored energy source fromcontributing to the displacement of the contents of the reservoir of thesyringe. In some variations, the rate control assembly may be configuredto do so by limiting or restricting the distal movement of a plunger orseal within the syringe cavity. The rate control assembly may beselectively and reversibly moved between open and closed configurations;in a closed configuration, the rate control assembly may limit orrestrict the stored energy source from contributing to the distalmovement of the seal within the syringe cavity. Together, the storedenergy source and the rate control assembly of the power assembly mayallow a user (a patient or another person) to direct the injectionprocess in an intuitive way by directing the injection by pressing theinjection device against a patient's skin, but the power assembly maysupply a supplemental injection force (or in some variations, the fullinjection force), such that the user does not need to provide the fullforce needed to carry out the injection.

As used throughout this specification, the term “proximal” refers to thedirection away from the needle of the syringe. The term “distal” refersto the direction of the needle of the syringe.

One embodiment of an injection device 100 is depicted in FIGS. 1 and2A-2N, comprising a housing 102 which contains a syringe 104 and a powerassembly 106. In some embodiments, the housing 102 may comprise aproximal housing 108 and a distal housing 110. As described above, theproximal housing 108 and distal housing 110 may be configured to fitslidably together to form a cavity 146. The syringe 104 and powerassembly 106 may be located within the cavity 146. It should beappreciated that while the distal housing 110 is shown to fit slidablywithin the proximal housing 108 in FIGS. 1 and 2A-2N, in othervariations the proximal housing may fit slidably within the distalhousing. In still other variations, the housing may only comprise aproximal housing, with a syringe projecting distally from the proximalhousing, or only distal housing, with a plunger or other actuatorprojecting distally or otherwise found on the proximal end of the distalhousing. The housing 102 may be configured to be moved between anextended configuration (shown in FIGS. 1 and 2A-2D), through a range ofintermediate configurations (for example, the configuration shown inFIGS. 2G-2J), and to a compressed configuration, or toward a compressedconfiguration (shown in FIGS. 2K-2N) by moving the proximal housing 108distally relative to the distal housing 110. In a retractedconfiguration, the proximal housing 108 is pushed over the distalhousing 110, or otherwise overlaps or telescopes with the distal housing110, and achieves a shorter overall housing length. In some variations,when in an extended configuration, the length of the housing 102 may beless than about 150 mm, about 160 mm, about 170 mm, about 180 mm, about190 mm, or about 200 mm. In other variations, the length of the housing102 may be greater than about 200 mm. In some variations, when in anextended configuration, the length of the housing 102 may be about 150mm to 155 mm, about 155 mm to 160 mm, about 160 mm to 165 mm, or about165 mm to about 170 mm.

In some variations, the housing 102 may comprise one or more elementsfor preventing or resisting the housing 102 from being moved back towardan extended configuration once initial compression has begun. Forexample, the housing 102 may comprise a one-way ratchet mechanismbetween proximal housing 108 and distal housing 110. As another example,the distal housing 110 may comprise a groove (not shown) extendingaround its circumference. The groove which may have a distal faceorthogonal to the surface of the distal housing 110, and a proximallyangled proximal face. An elastomer loop (e.g., an O-ring) (not shown)may reside in the groove. Due to the shape of the groove, if theproximal housing 108 moves proximally relative to the distal housing 110(i.e., the housing 102 is moved towards an extended configuration), theelastomer loop may be pulled along the proximal face, preventing furthermotion. As yet another example, the injection device 100 may comprise asharp prong (not shown) fixed relative to the distal housing 110 andangled distally, which may travel along the inside of the proximalhousing 108. In some variations, the sharp prong may travel along agroove on the inside of the proximal housing 108. The sharp prong may beconfigured to travel proximally relative to the proximal housing 108 asthe proximal housing 108 moves distally, but the sharp prong may not beable to move distally relative to the proximal housing 108, and thus mayresist movement of the housing 102 toward an extended configuration. Insome variations, the sharp prong may be attached to or integral to thesyringe sleeve 430 (described below). In some of these variations, thesharp prong may be attached to or integral to the proximal lip 454 ofthe syringe sleeve 430 (described below). In some variations, theproximal housing 108 and/or distal housing 110 may comprise one or moreelements to resist rotation of the proximal housing 108 and distalhousing 110 relative to each other, such as the clocking mechanismsdescribed in more detail below. In other variations, the proximalhousing 108 and distal housing 110 may be able to be rotated relative toeach other.

The distal housing 110 may further comprise a nose 116 at the distal end114, which may have a tapered shape as shown in FIGS. 1 and 2A-2N, butneed not. In still other variations, the nose may generally maintain thesame size and/or shape as the rest of the distal housing, along itslongitudinal length. Or, the nose may have a flared shape wherein thenose has a larger cross-sectional shape than the rest of the distalhousing and/or proximal housing. In some variations, the flared shapemay help the user maintain the injection device 100 in a perpendicularposition with respect to the surface of the injection site, slippage ofthe injection device 100 as download pressure is being applied by theuser, and/or may help allow the tissue to remain relatively flat duringthe injection process. In some variations, the flared shape may be agradual outward flaring of the nose, a schematic example of which isshown in FIG. 25A; in other variations, the nose may comprise a flatportion at its distal end having a larger cross-sectional shape than therest of the distal housing and/or proximal housing (e.g., a flat, disk,oval, ellipse, or the like), a schematic example of which is shown inFIG. 25B. These portions of the nose may be symmetric about the distalhousing, or in other variations it may be asymmetric about the distalhousing. Additionally or alternatively, the proximal housing maycomprise a flared portion at its distal end, having a largercross-sectional shape than the rest of the proximal housing, a schematicexample of which is shown in FIG. 25C. This may assist the user gripand/or apply force to the proximal housing.

The nose 116 may comprise a distal opening 112 at its distal end 158,through which the needle 406 of the syringe 104 may be extended, asdescribed below. In some variations, the nose 116 may be a separatecomponent of distal housing 110, while in other variations it may beintegral to distal housing 110. Similarly, the proximal housing 108 mayhave an end cap 118 at its proximal end 120. In some variations, the endcap 118 may be a separate component of proximal housing 108, while inother variations it may be integral to proximal housing 108. Theproximal housing 108 may optionally further comprise a grip (not shown),which may be configured to enhance a user's ability to hold onto orpress the proximal housing 108. In some variations, the grip may have anergonomic shape and/or a material that may enhance a user's ability tohold onto or press the proximal housing 108, such as a rubber grip.While shown in FIGS. 1 and 2A-2N as each having a substantiallycylindrical shape, the proximal housing 108 and distal housing 110 mayhave any suitable shape (e.g., having an elliptical cross-section,oblong cross-section, ovoid cross-section, square cross-section,rectangular cross-section, triangular cross-section, etc.). In somevariations, the maximum diameter (or maximum distance transverse to thelongitudinal axis) of the housing 102 may be less than about 20 mm,about 22 mm, about 24 mm, about 26 mm, about 28 mm, about 30 mm, about32 mm, about 34 mm, about 36 mm, about 38 mm, or about 40 mm. In somevariations, the maximum diameter (or maximum distance transverse to thelongitudinal axis) of the housing may be about 20 mm to 25 mm, about 25mm to 30 mm, about 30 mm to 35 mm, or about 35 mm to about 40 mm. Insome embodiments, the proximal housing 108 and/or distal housing 110 mayoptionally comprise one or more anti-roll elements (not shown). In somevariations, the anti-roll elements may comprise a planar region on theoutside of proximal housing 108. In some variations, rolling of thehousing 102 may be resisted by the housing 102 having a non-circularcross-sectional shape, such as an elliptical shape or other non-circularshape discussed above, or by the rigid needle shield (discussed below)having an asymmetric shape. The proximal housing 108 and distal housing110 may comprise any suitable materials, such as but not limited to oneor more plastic or metal materials.

In some variations, at least a portion of the distal housing 110 maycomprise a viewing region 124 allowing the syringe 104 to be seen fromoutside the housing 102. In some variations, this may allow the user tovisually monitor the progress or completion of the injection (e.g., invariations in which the syringe body also comprises a viewing region oris otherwise transparent or translucent (e.g. as a result of beingcomprise of a transparent or translucent materials, such as a glass orplastic), by visualizing the position of the plunger or seal within thesyringe cavity). In other variations, both the proximal housing 108 anddistal housing 110 may comprise a viewing region, only the proximalhousing 108 may comprise a viewing region, or neither the proximalhousing 108 nor the distal housing 110 may comprise a viewing region.The viewing region(s) (e.g., viewing region 124) may comprise atranslucent or transparent material, such as but not limited to a glassor plastic. In other variations, the viewing region(s) (e.g., viewingregion 124) may be an opening (e.g., an opening in the distal housing110). In some other variations, a viewing region may be used as anopening (open or covered) to replace the syringe component of the devicefor re-use. In some variations, the viewing region(s) may extend aroundthe full circumference of the proximal housing 108 and/or distal housing110, as shown in FIG. 1. In some variations, the viewing region(s) maycomprise substantially all of the distal housing 110, excluding the nose116, as shown in FIG. 1. In other variations, the viewing region(s) mayextend around a portion of the circumference of the proximal housingand/or distal housing.

In some variations, the housing 102 may optionally further comprise acap. FIGS. 2A-2B show two orthogonal cross-sectional views of theinjection device 100 before use with a cap 148 attached. The cap 148 maybe configured to fit slidably over the distal housing 110 and may coverthe distal opening 112 of nose 116. The cap 148 may be removed byapplying force to separate the cap 148 and the remainder of the housing102. In some variations, this can be done by holding the proximalhousing 108 with one hand and the cap 148 with another hand and pullingin opposite directions. In some variations, the cap 148 may furtherserve to remove the rigid needle shield 422. The cap 148 may beconnected to the rigid needle shield 422 in any suitable manner, suchthat removing the cap may also remove the rigid needle shield 422. Forexample, the cap 148 may comprise an inside proximal protrusion that mayfit around the outside of the rigid needle shield 422. The proximalprotrusion may be substantially cylindrical, but may have other shapes.The proximal protrusion may comprise an inwardly facing lip or lips thatmay fit into a recess or hook (or recesses or hooks) on the outside ofthe rigid needle shield 422. When the cap 148 is separated from theremainder of the housing 102, the rigid needle shield 422 may also beseparated from the syringe 104 due to force on the rigid needle shield422 from the inwardly facing lip. In some variations, the proximalprotrusion may be flexible (e.g., due to a cut-out) to allow the cap tobe installed over the distal housing 110 and rigid needle shield 422. Insome variations, the cap may comprise a viewing region, which maycoincide with the viewing region of the distal housing, when the cap isattached to the remainder of the housing.

FIGS. 2A-2N depict longitudinal cross-sectional views of the injectiondevice 100 of FIG. 1 in various stages during use. FIGS. 2A-2B show twoorthogonal cross-sectional views of the device before use. FIGS. 2C-2Dshow two orthogonal cross-sectional views of the device with the rigidneedle shield and cap removed. FIGS. 2E-2F show two orthogonalcross-sectional views of the device with the syringe partially movedtoward an extended position. FIGS. 2G-2H show two orthogonalcross-sectional views of the device with the syringe in an extendedposition. FIGS. 2I-2J show two orthogonal cross-sectional views of thedevice with the plunger partially moved toward a distal position withinthe syringe cavity. FIGS. 2K-2L two orthogonal cross-sectional views ofthe device with the plunger moved to the distal position within thesyringe cavity. FIGS. 2M-2N show two orthogonal cross-sectional views ofthe device with the needle shroud extended. The nose 116 may comprise aneedle safety assembly 200. In some variations, the needle safetyassembly 200 may comprise an extendable needle shroud 202 that protectsthe needle 406 after the injection is completed or terminated, a biasingelement 218, and a locking assembly 226. The needle safety assembly 200may be movable between a retracted position (shown in FIGS. 1, 2A-2L,and 3A-3D) and an extended position (shown in FIGS. 2M-2N and 3E-3F). Inthe retracted position, the needle shroud 202 may allow the needle 406of the syringe 104 to be exposed when the syringe 104 is in an extendedposition, as described in detail below. Thus, in the retracted position,the distal end 212 of the needle shroud 202 may be located proximally tothe distal tip 424 of the needle 406 when the syringe 104 is in anextended position. In an extended position, the needle shroud 202 mayshield the needle 406 from exposure when the syringe 104 is in anextended position; for example, the needle shroud 202 may resistinsertion of the needle 406 in a patient's tissue or resist contactbetween the needle 406 and tissue. Thus, in an extended position, thedistal end 212 of the needle shroud 202 may be located distally to thedistal tip 424 of the needle 406 when the syringe 104 is in an extendedposition. In some variations, the displacement of the needle shroud 202between retracted and extended positions may be about 6 mm to 8 mm,about 8 mm to 10 mm, about 10 mm to 12 mm, about 12 mm to 14 mm, orabout 14 mm to 16 mm.

As shown in FIGS. 3A-3D, the needle shroud 202 may fit slidably withinthe nose 116. In the variations shown in FIGS. 3A-3F, when the needlesafety assembly 200 is in a retracted position, the distal end 212 ofthe needle shroud 202 may be flush with the distal end 158 of the nose116, while in an extended position, the distal end 212 of the needleshroud 202 may be distal to the distal end 158 of the nose 116. Itshould be appreciated that in other variations, in a retracted position,the distal end 212 of the needle shroud 202 may be proximal to thedistal end 158 of the nose 116, or in other variations, it may be distalto the distal end 158 of the nose 116 in a retracted position.

The needle shroud 202 may have a proximal opening 204 and a distalopening 206, with a lumen 208 extending between the proximal opening 204and distal opening 206. The needle shroud 202 may have a longitudinalaxis 210 aligned with the longitudinal axis 144 of the housing 102.While the needle shroud 202 is shown as having a cylindrical shape inFIGS. 3A-3F, it should be appreciated that the needle shroud may haveother shapes (e.g. an elliptical cross-section, oblong cross-section,ovoid cross-section, square cross-section, rectangular cross-section,triangular cross-section, or the like). In some variations, the needleshroud 202 may optionally comprise a stop (not shown) to resist theneedle shroud 202 being disconnected from the nose 116 (e.g., to resistthe needle shroud 202 sliding distally away from and disengaging withthe nose 116). Additionally or alternatively, the needle shroud 202 maycomprise a distal lip 216 to hold the biasing element 218, describedbelow. In some variations, the needle shroud 202 may comprise a plasticmaterial, but it should be appreciated that the needle shroud 202 maycomprise any suitable material. The needle shroud 202 may be opticallyopaque, translucent, or transparent. The needle shroud may alsooptionally comprise apertures or cutouts to permit partial visualizationof the needle during or after the injection procedure.

The biasing element 218 may be configured to bias the needle safetyassembly 200 toward an extended position. The biasing element 218 mayhave a compressed configuration and an expanded configuration. Thebiasing element 218 may be in a compressed configuration when the needlesafety assembly 200 is in a retracted configuration, and the biasingelement 218 may be in an expanded configuration when the needle safetyassembly 200 is in an extended position. In some variations, the biasingelement 218 may comprise a compression spring 220. When the compressionspring 220 is in a compressed configuration, the compression spring 220at its proximal end 222 may be connected to or in contact with a portionof the distal housing 110 or nose 116, and at its distal end 224 may beconnected to or in contact with a portion of the needle shroud 202. Thebiasing element 218 (e.g., compression spring 220) may thus bias theneedle shroud 202 distally away from the distal housing 110 and nose 116through the distal opening 112 of the nose 116. In the variation shownin FIGS. 3A-3F, the compression spring 220 may have a cylindrical shapeand may fit within the lumen 208 of the needle shroud 202. The proximalend 222 of the compression spring 220 may contact a ledge 156 extendingradially inward from the distal end 114 of the distal housing 110, andthe distal end 224 of the compression spring 220 may contact the lip 216extending radially inward from the needle shroud 202. While the lip 216is shown as located at the distal end 212 of needle shroud 202 in FIGS.3A-3F, it should be appreciated that in other variations a lip mayextend from a location proximal to the distal end 212 of the needleshroud 202. In some variations, the proximal end 222 of the compressionspring 220 may be fixedly attached to the distal end 114 of distalhousing 110, but it need not be (e.g., it may rest against the distalend 114 of the distal housing 110 but be unattached). Similarly, in somevariations, the distal end 224 of the compression spring 220 may befixedly attached to the needle shroud 202, but it need not be (e.g., itmay rest against a portion of the needle shroud 202 but be unattached).It should be appreciated that in other variations the biasing element218 may not comprise a compression spring 220 and may instead compriseother forms of biasing elements (e.g., an extension spring, torsionspring, or the like) configured so as to bias the needle shroud 202distally away from the distal housing 110. In some variations, thebiasing element 218 may provide about 1N, about 2N, about 3N, about 4N,about 5N, about 6N, about 7N, or about 8N of biasing force.

The locking assembly 226 may hold the needle shroud 202 in a retractedposition and/or in an extended position. In some variations, the lockingassembly 226 may comprise one or more latches 228 that may be configuredto connect the needle shroud 202 to the syringe 104. While in theembodiment of FIGS. 3A-3F, the locking assembly 226 may comprise fourlatches 228 evenly spaced around the needle shroud 202, it should beappreciated that in other variations, the locking assembly 226 maycomprise fewer or more latches and may have different positioning (e.g.,one, two, three, five, or six latches, etc., which may or may not beevenly spaced from each other). In some variations, the latches 228 maybe integral to the needle shroud 202. The latches 228 may each comprisean elongate portion 230 extending proximally from the needle shroud 202,and a tab 234 extending from the elongate portion 230. In somevariations, the elongate portions 230 may have different lengths. Theelongate portion 230 may extend proximally from the proximal opening 204of the needle shroud 202, and the tab 234 may extend inwardly from theproximal end of the elongate portion 230. As shown in FIGS. 3A-3B, thelatches 228 may be configured to mate with the syringe sleeve 430(described below), such that when mated, the latches 228 resist motionof the needle shroud 202 relative to the distal housing 110. The syringesleeve 430 may comprise four proximal slots 168, which may be located onthe syringe sleeve 430 such that when the tabs 234 of the latches 228are mated with the proximal slots 168, the needle shroud 202 may belocated in a retracted position. When the tabs 234 are mated with theproximal slots 168, the elongate portion 230 of the latches 228 may beflush against the outer surface 458 of the syringe sleeve 430, while thetabs 234 of the latches 228 may be inserted radially into the proximalslots 168. The locking assembly 226 may resist distal motion due to abiasing force from the biasing element 218 because of the proximallyoriented force applied to the distal surface of the tabs 234 by thedistal surface of the proximal slots 168.

As shown in FIGS. 3C-3D, the locking assembly 226 may be configured suchthat the needle shroud 202 may be unlocked from a retracted position(e.g., the locking assembly 226 may no longer hold the needle shroud 202in a retracted position) by distal motion of the syringe 104. In somevariations, the tabs 234 may be configured such that they can bereleased from the proximal slots 168 by distal movement of the syringe104 relative to the syringe sleeve 430. For example, in the variationshown in FIGS. 3A-3F, the tabs 234 may have a triangular, proximallytapering shape. Thus, as the syringe 104 is moved distally within thesyringe sleeve 430, the distal end 418 of the outer surface 468 of thesyringe body 402 may engage the inner surface 236 of the tabs 234protruding through the proximal slots 168. As the outer surface 468 ofthe syringe body 402 continues to slide distally along the inner surface460 of the syringe sleeve 430 (described below), the outer surface 468of the syringe body 402 gradually pushes the tabs 234 further radiallyout of the proximal slots 168. Once the outer surface 468 of the syringebody 402 has fully pushed the tabs 234 radially out of the proximalslots 168, the tabs 234 may no longer be mated with the proximal slots168 and may no longer resist distal motion of the needle shroud 202relative to the distal housing 110. It should be appreciated that whilethe latches in the embodiment of FIGS. 3A-3F are connected (or integral)to the needle shroud 202 and fit into slots in the syringe sleeve 430,in other variations, the latches may be connected (or integral) to thesyringe sleeve and may fit into slots in the needle shroud. For example,the inner surface of the syringe sleeve may comprise inwardly facingtabs, which may extend inwardly through slots in the needle shroud, suchthat they may protrude radially within the inner surface of the syringesleeve. As in the embodiment in FIGS. 3A-3F, distal movement of thesyringe may cause the outer surface of the syringe body to push the tabsradially outward through the slots to an extent sufficient to cause thetabs to no longer resist distal motion of the needle shroud relative tothe distal housing.

When the needle shroud 202 is unlocked from a retracted position, if aforce is then applied that is configured to urge the needle shroud 202from a retracted position to an extended position (e.g., a biasing forcefrom the biasing element 218), the needle shroud 202 may move from aretracted position to an extended position. However, the forceconfigured to urge the needle shroud 202 from a retracted position to anextended position may be counterbalanced or partially or completelyopposed by a proximally directed force on the needle shroud 202. Forexample, in the variation shown in FIGS. 3A-3F, the distal end 212 ofthe needle shroud 202 is configured to be pressed against a patient'stissue during an injection. Thus, the tissue may apply a force to thedistal end 212 of the needle shroud 202, partially or fullycounteracting the biasing force from the biasing element 218 (e.g.,compression spring 220) while the injection device 100 is pressedagainst the tissue. This may resist the needle shroud 202 moving from aretracted position to an extended position, even when the needle shroud202 is unlocked from a retracted position. However, if the injectiondevice 100 is then moved away from the tissue, there may no longer be aforce from the tissue to counteract the biasing force from the biasingelement 218, and as a result, the needle shroud 202 may move from aretracted position to an extended position, as shown in FIGS. 3E-3F.

In some variations, such as the variation of FIGS. 3A-3F, the lockingassembly 226 may be configured such that the needle shroud 202 may beunlocked from a retracted position just before the distal tip 424 of theneedle 406 of the syringe 104 extends from the distal end 158 of thenose 116, as shown in FIGS. 3C-3D. Thus, at any time the needle 406 isexposed such that it is capable of piercing or otherwise contacting apatient's tissue, the needle shroud 202 is unlocked from a retractedposition. The exposure of the needle 406 for injection may thereforeonly be maintained by maintaining a proximal force on the distal end 212of the needle shroud 202 to hold it in a retracted position (e.g. bypressing the distal end 212 of the needle shroud 202 against a patient'stissue); once the proximal force is removed (e.g., by moving theinjection device 100 away from a patient's tissue), the needle shroud202 may move into an extended position, which may resist piercing of apatient's tissue by the needle 406 or resist contact between the needle406 and a patient's tissue.

In some variations, the needle shroud 202 of the needle safety assembly200 may additionally or alternatively be configured to be locked in anextended position once moved to an extended position. That is, theneedle shroud 202 may be configured such that once it enters an extendedposition, it may be unable to return to a retracted position. In somevariations wherein the locking assembly comprises one or more latches,the same latches may be used to lock the needle shroud 202 in anextended position. In some of these variations, as shown in FIGS. 3E-3F,the syringe sleeve 430 may comprise four distal slots 176 configured tomate with the tabs 234 of the latches 228 of the locking assembly 226.The distal slots 176 may be located on the syringe sleeve 430 tocoincide with the position of the tabs 234 when the needle shroud 202 isin an extended position. When the needle shroud 202 moves into anextended position, the tabs 234 on the latches 228 may mate with thedistal slots 176. When the tabs 234 on the latches 228 are mated withthe distal slots 176, the locking assembly 226 may resist motion of theneedle shroud 202 relative to the syringe sleeve 430, and in turn, maycause the locking assembly 226 to resist motion of the needle shroud 202relative to the distal housing 110. Once locked in an extended position,the needle shroud 202 may, for example, resist proximal force on thedistal end 212 of the needle shroud 202 (e.g., from tissue pressedagainst the distal end 212 of the needle shroud 202) tending to urge theneedle shroud 202 proximally toward a retracted position, and/or theneedle shroud 202 may resist distal force applied to it (e.g., from thebiasing element 218) tending to urge the needle shroud 202 further awayfrom the distal housing 110. In variations of the injection deviceconfigured to lock in an extended position, this feature may limit theability of a needle to extend from the distal end of the nose to pierceor otherwise contact tissue or other surfaces after the injection devicehas been removed from a patient's tissue. This may make the injectiondevice safer for the user and/or patient by limiting accidentalneedlesticks after injection has been fully or partially completed.However, it should be appreciated that in other variations, the needleshroud may not be configured to lock when in an extended position (e.g.,in some variations, the needle shroud 202 may retract from an extendedposition in response to distal force).

In some variations, the needle safety assembly 200 may provide feedbackto the user. In some variations, this feedback may include a biohazardindicator, such as a biohazard symbol located on the outside surface ofthe needle shroud 202, which may be visible when the needle shroud 202is in an extended position. Additionally or alternatively, all or aportion of the needle shroud 202 may be colored (e.g. red, yellow,orange, green, magenta, blue, or the like) in order to indicate orsignal to the user that the injection device 100 has been used.

The housing 102 may comprise an indicator to indicate the progress orcompletion of the injection. In one variation, the indicator may have arange of configurations corresponding to various levels of progress ofthe injection. In some such variations, the configurations may havedifferent visual, tactile, or auditory perceptions, such as but notlimited to color, numerical, or ordinal cues or indicia, or the positionof the proximal housing 108 relative to the distal housing 110. In thesame or other variations, the transition between the inactivatedconfiguration and the activated configuration, and/or the transitionbetween the configurations, may produce visual, tactile, or auditoryalerts, such as but not limited to color, numerical, or ordinal cues orindicia, or the position of the proximal housing 108 relative to thedistal housing 110.

In some variations, the indictor may alert the user that the full dosehas been displaced from the reservoir 414 of the syringe 104 and/or thatthe seal 410 has traveled the full length of the reservoir 414 to thedistal end 462 of the syringe cavity 404 (described below). Additionallyor alternatively, the end-of-dose indicator may alert the user thatnearly (e.g., greater or equal to about 85%, greater or equal to about90%, greater or equal to about 95%, or more) the full dose has beendisplaced from the reservoir 414 of the syringe 104 and/or that the seal410 has traveled nearly (e.g., greater or equal to about 85%, greater orequal to about 90%, greater or equal to about 95%, or more, or withinabout 1 mm of full displacement, about 2 mm of full displacement, about3 mm of full displacement, or about 4 mm of full displacement, etc.) thefull length of the reservoir 414 to the distal end 462 of the syringecavity 404.

FIGS. 4A-4C illustrate longitudinal cross-sectional views of a proximalportion of the injection device of FIG. 1, showing the end-of-doseindicator 300 having a different visual appearance associated with theinactivated (FIG. 4A) and activated (FIG. 4C) configurations. Theindicator 300 may be seen through the housing 102 in the activatedconfiguration, while not seen through the housing 102 in the inactivatedconfiguration. In some variations, at least a portion of the housing 102may be translucent, transparent, or comprise an opening to allow thevisual appearance of the indicator 300 to be different between theactivated and inactivated configurations. For example, the indicator 300may be seen when in an activated configuration through the end cap 118of the proximal housing 108, which may comprise a transparent ortranslucent material. While in the variation of FIGS. 4A-4C thetransparent or translucent region is in end cap 118, it should beappreciated that in other variations the indicator 300 may be seenthrough other portions of the housing 102.

In the variation shown in FIGS. 4A-4C, the indicator 300 may comprise amain body 302, a release member 308, and a biasing element 320. The mainbody 302 and end cap 118 of the proximal housing 108 may be configuredsuch that when the main body 302 is adjacent to the inner surface 186 ofthe end cap 118, at least a portion of the main body 302 may be seenfrom outside the end cap 118 through a viewing portion. In somevariations, at least a portion of the main body 302 may have a color orpigment that may be capable of being more easily noticed, such as butnot limited to red, yellow, orange, green, magenta, blue, and the like.In order for the main body 302 to be seen through at least a portion ofend cap 118, in some variations, at least a portion of the end cap 118may be translucent. In variations in which a portion of the end cap 118is translucent, the level of translucency may be such that the coloringof the main body 302 may be perceived through the end cap 118 only whenthe main body 302 is adjacent or nearly adjacent to the viewing portion.In other variations, the end cap 118 may comprise a transparent or openregion configured such that the main body 302 is only visible throughthe viewing portion when the main body 302 is adjacent to thetransparent or open region, for example, because of the viewing angle.For instance, in some such variations, the viewing portion may comprisea transparent region around the circumference of the end cap 118, andthe main body 302 of the indicator 300 may only be visible through theviewing portion when aligned adjacent to the viewing portion. The mainbody 302 of the indicator 300 may also comprise a lumen 304 therethroughto allow a portion of the ram 502 (described below) to pass through themain body 302.

The biasing element 320 may be configured to bias the indicator 300toward an activated configuration. The biasing element 320 may have acompressed configuration and an expanded configuration. The biasingelement 320 may be in a compressed configuration when the indicator 300is in an inactivated configuration, and the biasing element 320 may bein an expanded configuration when the indicator 300 is in an activatedconfiguration. As shown in FIGS. 4A-4C, in some variations the biasingelement 320 may comprise a compression spring 322. The proximal end 324of the compression spring 322 may be connected to or in contact with themain body 302 of the indicator 300, and the distal end 326 of thecompression spring 322 may be connected to or in contact with theinterlocker 436 (described below). The biasing element 320 may thus biasthe main body 302 of the indicator 300 away from the ram 502.

As shown in FIG. 4A, the release member 308 may hold the indicator 300in an inactivated configuration until released. The release member 308may comprise an elongate portion 312 and a locking portion 310. Theelongate portion 312 may connect the main body 302 and the lockingportion 310, and the locking portion 310 may extend radially outwardfrom the distal end of the elongate portion 312. When the indicator 300is in an inactivated configuration, the radially outer tip of thelocking portion 310 may fit within an indicator recess 328 in theinterlocker 436. Radially outward pressure from the plunger 510 on theinner end of the locking portion 310 may resist the locking portion 310from moving radially inward to emerge or disengage from the recess 328.The protrusion of the outer tip of the locking portion 310 into theindicator recess 328 may result in a distally directed force on thelocking portion 310 from the proximal surface of the recess 328, whichmay counteract the biasing force of the compression spring 322, andwhich may thus hold the indicator 300 in an inactivated configuration.

When the release member 308 is released, the indicator 300 may no longerbe held in an inactivated configuration, as shown in FIG. 4B. Therelease member 308 may be released by the distal motion of the ram 502as the injection proceeds (as described in more detail below). As theram 502 moves distally relative to the interlocker 436, the plunger 510may move distally relative to the locking portion 310 of the releasemember 308, until the plunger 510 may be fully distal to the lockingportion 310, as shown in FIG. 4B. At this point, the plunger 510 may nolonger contact the inner end of the locking portion 310 to resist thelocking portion 310 from moving radially inward to emerge or disengagefrom the recess 328. As a result, the locking portion 310 may moveradially inward to emerge or disengage from the recess 328, and theproximal surface of the recess 328 may no longer provide a distallydirected force on the locking portion 310 to counteract the biasingforce from the compression spring 322, thus releasing the release member308. Once released, the biasing force from the compression spring 322may cause the indicator 300 to move proximally relative to theinterlocker 436 and toward an activated configuration, as shown in FIG.4C.

FIGS. 4D-4E illustrate cut-away elevational side views of a proximalportion of another embodiment of an injection device showing anotherexample of an end-of-dose indicator in inactivated (FIG. 4D) andactivated configurations (FIG. 4E). In the embodiment of FIGS. 4D-4E,the indicator 300 may, like the embodiment of FIGS. 4A-4C, comprise amain body 2302, a release member 2308, and a biasing element 2320, butthe proximal end 2324 of the compression spring 2322 may be connected toor in contact with an inner lip 2306 on the main body 2302 of theindicator 2300, and the distal end 2326 of the compression spring 2322may be connected to or in contact with the arms 506 of the ram 2502. Therelease member 2308 may comprise one or more latches 2310 that may matewith a slot or other form of recess in the arm 2506 of the ram 2502.When the latches 2310 are mated with the slots or recesses, the releasemember 2308 may resist distal motion of the main body 2302 of theindicator 2300 relative to the ram 502 (e.g., due to a biasing forcefrom the biasing element 2320). If the latches 2310 are released fromthe slots or recesses, a force from the biasing element 2320 may causethe indicator 2300 to move into an activated configuration, as shown inFIG. 4E. In the embodiment shown in FIGS. 4D-4E, for example, therelease member 2308 may comprise two latches 2310. Each latch 2310 mayextend distally from the main body 2302 of the indicator 2300. Eachlatch 2310 may be configured to mate with an indentation ridge 2524 onthe outer surface of an arm 2506 of the ram 2502. When the latches 2310are mated with the indentation ridge 2524, the proximal side of theindentation ridge may resist proximal motion of the latch 2310 and thusof the main body 2302 of the indicator 2300 due to the biasing forcefrom the compression spring 2322. If the latches 2310 are released fromthe indentation ridges 2524, however, the biasing force from thecompression spring 2322 may urge apart the ram 2502 and the indicator2300, moving the main body 2302 of the indicator 2300 towards the endcap 2118 of the proximal housing 2108, which may cause the indicator2300 to be visible through the end cap 2118. The tabs 2103 may beconfigured to be released from the indentation ridge 2524 by distalmovement of the ram 2502 relative to the proximal housing 2108 and endcap 2118. When the ram 2502 has moved distally such that the full dosehas been displaced from the reservoir of the syringe and/or nearly thefull dose has been displaced from the reservoir of the syringe thelatches 2310 may be pushed out of the indentation ridges 2524, movingthe indicator 2300 to an activated configuration, as shown in FIG. 4E.

While the indicators in FIGS. 4A-4E are end-of-dose indicators, in othervariations, the indicator may be configured to convey the progress ofthe injection at one or more points throughout the injection. Forexample, in some variations, the proximal housing 108 and/or distalhousing 110 may comprise a viewing region (e.g., a transparent ortransparent region, or an opening) such that the location of theinterlocker 436 (described below) may be viewed through the viewingregion. The location of the interlocker 436 relative to the housing 102may indicate the progress of the injection. In some of these variations,the interlocker 436 may be colored or comprise a colored region to bemore easily visible through the viewing region. In other variations, aseparate component, which may also be colored or comprise a coloredregion, may be attached to the interlocker 436, which may be seenthrough the viewing region.

As described briefly above, in general, the syringe 104 may comprise asyringe body defining a syringe cavity, a seal slidably disposed withinthe lumen of the syringe cavity defining a reservoir that may hold aformulation comprising a therapeutic or diagnostic agent, a ramcomprising a plunger that may fit slidably within the syringe cavity,and a needle at the distal end of the syringe body. The needle may beconfigured to pierce the tissue of a patient receiving an injection, andmay have a lumen therethrough to deliver the contents of the reservoirto the patient's tissue. Movement of the seal within the syringe cavitydistally may cause the contents of the reservoir to be displaced throughthe lumen of the needle.

Returning to FIGS. 2A-2N, the syringe 104 may comprise, as brieflymentioned above, a syringe body 402, which may define a syringe cavity404. The syringe cavity 404 may be in fluid communication with the lumen408 of the needle 406, described in more detail below. A seal 410 may beslidably disposed within the syringe cavity 404 and may form an airtightseal with the inner surface 412 of the syringe body 402. The innersurface 412 of the syringe body 402 and the seal 410 may form areservoir 414 configured to contain a formulation, such as a solution,comprising a therapeutic or diagnostic agent. The seal 410 may limit thecontents of the syringe cavity 404 from flowing or otherwise movingproximally to the seal 410. If the seal 410 is moved distally relativeto and within the syringe cavity 404, the volume of the reservoir 414may be decreased. Thus, distal motion of the seal 410 relative to andwithin the syringe cavity 404 may cause the contents of the reservoir414 to be displaced through the lumen 408 of the needle 406. In somevariations, the reservoir 414 may be configured to contain a maximumvolume of about 1 mL, about 2 mL, about 3 mL, about 4 mL, or about 5 mL.In other variations, the reservoir 414 may be configured to contain amaximum volume of about 0.1 mL to 1 mL, 1 mL to 2 mL, 2 mL to 3 mL, 3 mLto 5 mL, 5 mL to 10 mL, 10 mL to 15 mL, 15 mL to 20 mL, 20 mL to 25 mL,or more. While the syringe 104 is shown as having a circularcross-section, and thus the syringe body 402 forms a barrel, in othervariations, the syringe 104 and its component parts may have anysuitable shape (e.g., having an elliptical cross-section, oblongcross-section, ovoid cross-section, square cross-section, rectangularcross-section, triangular cross-section, etc.).

The reservoir 414 formed by the inner surface 412 of the syringe body402 and the seal 410 may contain a formulation comprising one or moretherapeutic or diagnostic agents. In some variations, the therapeutic ordiagnostic agent may be a substance such as but not limited to a largemolecule, small molecule, or a biologic. In some variations, theformulation may further comprise one or more solvents, diluents, and/oradjuvants. The formulation may have any suitable viscosity. Generally,the formulation may have a viscosity of up to 10 cP, up to 20 cP, up to30 cP, up to 40 cp, up to 50 cP, up to 60 cP, up to 70 cP, up to 80 cP,up to 90 cP, or up to 100 cP. In some instances, the formulation mayhave a higher viscosity, such as up to 1,000 cP, up to 10,000 cP, or upto 50,000 cP. Examples of higher viscosity injectates include certaindermal fillers used for cosmetic or tissue bulking procedures, such asthe treatment of urinary incontinence. In some instances the formulationmay have a significantly higher viscosity (e.g., an even higherviscosity, such as up to 500,000 cP or higher.

In some variations, the therapeutic or diagnostic agent may be asubstance that may be used with patient populations for whom apower-assisted injection device as described herein may be beneficial,such as but not limited to patient populations having diseases ordisorders such as but not limited to multiple sclerosis, rheumatoidarthritis, cancers, Alzheimer's disease, or IgE-mediated disorders(e.g., allergic rhinitis, asthma (e.g., allergic asthma and non-allergicasthma), atopic dermatitis, allergic gastroenteropathy, hypersensitity(e.g., analphylaxis, urticaria, food allergies, etc.), allergicbronchopulmonary aspergillosis, parasitic diseases, interstitialcystitis, hyper-IgE syndrome, ataxia-telangiectasia, Wiskott-Aldrichsyndrome, thymic alymphoplasia, IgE myeloma and graft-versus-hostreaction). In some variations, the therapeutic or diagnostic agent may,but need not be, selected from beta interferons (e.g., BETAFERON®,AVONEX®, REBIF®, Extavia®), natalizumab (TYSABRI®), TNFα inhibitors(e.g., etanercept (ENBREL®), infliximab (REMICADE®), adalimumab(HUMIRA®), golimumab (SIMPONI®), and certolizumab pegol (CIMZIA®)),abatacept (Orencia®), anakinra (Kineret®), anti-CD20 antibodies (e.g.,rituximab (Rituxan®) or ocrelizumab), anti-IL-6 receptor antibodies(e.g., tocilizumab (Actemra®)), anti-IL-13 antibodies (e.g.,lebrikizumab), anti-CD20 antibodies (e.g., obinutuzumab), anti-HER2antibodies (e.g., trastuzumab), or an anti-Abeta antibodies (e.g.,crenezumab).

In some variations, the formulation may comprise a therapeuticallyeffective amount of a protein or proteins, such as but not limited togrowth hormone, including human growth hormone and bovine growthhormone; growth hormone releasing factor; parathyroid hormone; thyroidstimulating hormone; lipoproteins; α-1-antitrypsin; insulin A-chain;insulin B-chain; proinsulin; follicle stimulating hormone; calcitonin;luteinizing hormone; glucagon; clotting factors such as factor VIIIC,factor IX, tissue factor, and von Willebrands factor; anti-clottingfactors such as Protein C; atrial natriuretic factor; lung surfactant; aplasminogen activator, such as urokinase or tissue-type plasminogenactivator (t-PA, e.g., Activase®, TNKase®, Retevase®); bombazine;thrombin; tumor necrosis factor-α and -β; enkephalinase; RANTES(regulated on activation normally T-cell expressed and secreted); humanmacrophage inflammatory protein (MIP-1-α); serum albumin such as humanserum albumin; mullerian-inhibiting substance; relaxin A-chain; relaxinB-chain; prorelaxin; mouse gonadotropin-associated peptide; DNase;inhibin; activin; vascular endothelial growth factor (VEGF); receptorsfor hormones or growth factors; an integrin; protein A or D; rheumatoidfactors; a neurotrophic factor such as bone-derived neurotrophic factor(BDNF), neurotrophin-3, -4, -5, or -6 (NT-3, NT-4, NT-5, or NT-6), or anerve growth factor such as NGF-P; platelet-derived growth factor(PDGF); fibroblast growth factor such as aFGF and bFGF; epidermal growthfactor (EGF); transforming growth factor (TGF) such as TGF-α and TGF-β,including TGF-(31, TGF-β2, TGF-β3, TGF-β4, or TGF-β5; insulin-likegrowth factor-I and -II (IGF-I and IGF-II); des(1-3)-IGF-I (brainIGF-I); insulin-like growth factor binding proteins; CD proteins such asCD3, CD4, CD8, CD19 and CD20; erythropoietin (EPO); thrombopoietin(TPO); osteoinductive factors; immunotoxins; a bone morphogeneticprotein (BMP); an interferon such as interferon-α, -β, and -γ; colonystimulating factors (CSFs), e.g., M-CSF, GM-CSF, and G-CSF; interleukins(ILs), e.g., IL-1 to IL-10; superoxide dismutase; T-cell receptors;surface membrane proteins; decay accelerating factor (DAF); a viralantigen such as, for example, a portion of the AIDS envelope; transportproteins; homing receptors; addressins; regulatory proteins;immunoadhesins; antibodies; and biologically active fragments orvariants of any of the above-listed polypeptides. By “protein” is meanta sequence of amino acids for which the chain length is sufficient toproduce the higher levels of tertiary and/or quaternary structure. Insome of these variations, the protein which is formulated may beessentially pure and essentially homogeneous (i.e., free fromcontaminating proteins). “Essentially pure” protein means a compositioncomprising at least about 90% by weight of the protein, based on totalweight of the composition, preferably at least about 95% by weight.“Essentially homogeneous” protein means a composition comprising atleast about 99% by weight of protein, based on total weight of thecomposition.

In some variations, the formulation may comprise high concentrations oflarge molecular weight proteins, such as antibodies or immunoglobulins.The antibodies may, for example, be antibodies directed against aparticular predetermined antigen. In a specific aspect, the antigen isIgE (e.g., rhuMAbE-25, rhuMAbE-26 described in U.S. Pat. No. 6,329,509and WO 99/01556). Alternatively, the anti-IgE antibody may be CGP-5101(Hu-901) described in Corne et al., J. Clin. Invest. 99(5): 879-887(1997), WO 92/17207, and ATTC Deposit Nos. BRL-10706 and 11130, 11131,11132, 11133. Alternatively, the antigen may include: the CD proteinsCD3, CD4, CD8, CD19, CD20, CD34 and CD40; members of the HER receptorfamily such as EGF receptor, HER2, HER3 or HER4 receptor; 2C4, 4D5,PSCA, LDP-2, cell adhesion molecules such as LFA-1, Mac1, p150, 95,VLA-4, ICAM-1, VCAM and αv/β3 integrin including the α- and β-subunitsthereof (e.g., anti-CD11a, anti-CD18 or anti-CD11b antibodies); growthfactors such as VEGF; blood group antigens; flk2/flt3 receptor; obesity(OB) receptor; mp1 receptor, CTLA-4, and protein C. The antibodies mayalso be those that specifically bind to the antigenic targets disclosedin the following patent applications: U.S. Ser. No. 10/177,488, filed 19Jun. 2002; U.S. Ser. No. 09/888,257, filed 22 Jun. 2001; U.S. Ser. No.09/929,769, filed 14 Aug. 2001; U.S. Ser. No. 09/938,418, filed 23 Aug.2001; U.S. Ser. No. 10/241,220, filed 11 Sep. 2002; U.S. Ser. No.10/331,496, filed 30 Dec. 2002; U.S. Ser. No. 10/125,166, filed 17 Apr.2002; U.S. Ser. No. 10/127,966, filed 23 Apr. 2002; U.S. Ser. No.10/272,051, filed 16 Oct. 2002; U.S. Ser. No. 60/299,500, filed 20 Jun.2001; U.S. Ser. No. 60/300,880, filed 25 Jun. 2001; U.S. Ser. No.60/301,880, filed 29 Jun. 2001; U.S. Ser. No. 60/304,813, filed 11 Jul.2001; U.S. Ser. No. 60/312,312, filed 13 Aug. 2001; U.S. Ser. No.60/314,280, filed 22 Aug. 2001; U.S. Ser. No. 60/323,268, filed 18 Sep.2001; U.S. Ser. No. 60/339,227, filed 19 Oct. 2001; U.S. Ser. No.60/336,827, filed 7 Nov. 2001; U.S. Ser. No. 60/331,906, filed 20 Nov.2001; U.S. Ser. No. 60/354,444, filed 2 Jan. 2002; U.S. Ser. No.60/351,885, filed 25 Jan. 2002; U.S. Ser. No. 60/360,066, filed 25 Feb.2002; U.S. Ser. No. 60/362,004, filed 5 Mar. 2002; U.S. Ser. No.60/366,869, filed 20 Mar. 2002; U.S. Ser. No. 60/366,284, filed 21 Mar.2002; U.S. Ser. No. 60/368,679, filed 28 Mar. 2002; U.S. Ser. No.60/369,724, filed 3 Apr. 2002; U.S. Ser. No. 60/373,160, filed 16 Apr.2002; U.S. Ser. No. 60/378,885, filed 8 May 2002; U.S. Ser. No.60/404,809, filed 19 Aug. 2002; U.S. Ser. No. 60/405,645, filed 21 Aug.2002; U.S. Ser. No. 60/407,087, filed 29 Aug. 2002; U.S. Ser. No.60/413,192, filed 23 Sep. 2002; U.S. Ser. No. 60/419,008, filed 15 Oct.2002; U.S. Ser. No. 60/426,847, filed 15 Nov. 2002; U.S. Ser. No.60/431,250, filed 6 Dec. 2002; U.S. Ser. No. 60/437,344, filed 31 Dec.2002, U.S. Ser. No. 60/414,971, filed 2 Oct. 2002, U.S. Ser. No.60/418,988, filed 18 Oct. 2002 and Docket No. PR5035, filed 5 Feb. 2003.The term “antibody” as used herein may include monoclonal antibodies(including full length antibodies which have an immunoglobulin Fcregion), antibody compositions with polyepitopic specificity,multispecific antibodies (e.g., bispecific antibodies, diabodies, andsingle-chain molecules, as well as antibody fragments (e.g., Fab,F(ab′)2, and Fv).

In some variations, the therapeutic agent may be a subcutaneousformulation containing high concentrations of large molecular weightproteins, such as immunoglobulins. The immunoglobulins may, for example,be antibodies directed against a particular predetermined antigen, whichcan include, for example, IgE (e.g., rhuMAbE-25, rhuMAbE-26 andrhuMAbE-27 described in WO 99/01556); the CD proteins, such as, forexample, CD3, CD4, CD8, CD19, CD20, CD34 and CD83; members of the HERreceptor family such as EGF receptor, HER2, HER3 or HER4 receptor; celladhesion molecules such as LFA-1, Mol, p150,95, VLA-4, ICAM-1, VCAM andαv/β3 integrin including the α- and β-subunits thereof (e.g.,anti-CD11a, anti-CD18 or anti-CD11b antibodies) or integrin beta 7;growth factors such as VEGF; blood group antigens; flk2/flt3 receptor;obesity (OB) receptor; interleukins such as, for example, IL2, IL3, IL4,IL5, IL6 and IL6 receptor, IL13, IL17, IL21, IL22, IL23, IL24, IL26,IL27, IL30, IL32, IL34 and; beta-amyloid; interferons such asinterferons I and II, which can include the interferon alphas: IFNA1,IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14,IFNA16, IFNA17, IFNA21 and the interferon betas: IFN-beta 1 and IFN-beta3; anaphylatoxins or complement activators such as C2, C2a, C5, C5a; andprotein C.

Although the formulations comprising one or more therapeutic ordiagnostic agents are described above with respect to syringe 104 ofinjection device 100, it should be appreciated that the formulationsdescribed above may be injected with any of the variations of injectiondevices described herein, including injection devices 700 and 1300described below.

The syringe body 402 and seal 410 and/or plunger may comprise anysuitable materials, such as but not limited to glass (e.g., Type 1glass), a polymer (e.g. a rubber, such as putyl rubber), a metal, or thelike. In some variations, the material or materials of the syringe body402 and/or seal 410 may have properties so as to not substantiallyinteract with the therapeutic or diagnostic agent, resisting adhesion,and/or promoting stability and/or sterility or sterilizability of theformulation. In some variations, the syringe body may comprise acoating. In some variations, the coatings may comprise silicone oils,fluoropolymers (e.g., perfluoropolyether-based chemical coatings,polytetrafluoroethylene (TEFLON®)), or the like. For example, thesyringe body may comprise glass that may be siliconized on the insidesurface. In some variations, the syringe body 402 and/or seal 410 maycomprise materials that limit light transmission to the therapeutic ordiagnostic agent (i.e., materials that reflect or absorb light), such asbut not limited to materials that block UV light and/or light at givenvisible wavelengths (e.g., amber-tinted materials), black-out materialsblocking all light, and foil linings. The material(s) may be selectedfor their specific colors, color change resistance (due to aging, due toexposure to the formulation, or due sterilization), leach resistance, inregard to some general or specific formulation characteristics. In somevariations, the syringe body 402 may comprise a translucent ortransparent material, such that the contents of the syringe body 402 canbe viewed through the material. In some variations, the shelf life ofthe therapeutic or diagnostic agent within the injection device 100 maybe up to about 1 year, about 2 years, about 3 years, about 4 years, orabout 5 years.

The needle 406 of the syringe 104 may be attached to the distal end ofthe syringe body 402 of the syringe 104. The proximal end 416 of theneedle 406 may be secured to the distal end 418 of the syringe body 402,such that the proximal end 416 of the lumen 408 of the needle 406 is influid communication with a distal opening 420 at the distal end 418 ofthe syringe body 402. The distal end 418 of the needle 406 may have apointed shape configured to pierce tissue. The needle 406 may thus beconfigured allow the formulation within the reservoir 414 to flow outthrough the distal opening 420 in the syringe body 402, through thelumen 408 of the needle 406, and into tissue, when the needle 406 isinserted into tissue. The length and gauge of the needle 406 may beappropriate for the intended use. For example, in some variations thesyringe 104 may comprise needle sizes up to, or including but notlimited to 7 gauge, 9 gauge, 11 gauge, 13 gauge, 15 gauge, 17 gauge, 19gauge, 21 gauge, 23 gauge, 25 gauge, 27 gauge, 29 gauge, 31 gauge, and33 gauge needles, and lengths including those up to about 3 mm, 4 mm, 6mm, 8 mm, 10 mm, 15 mm, 20 mm, 30 mm, 40 mm or more. The needle maycomprise any suitable material, including but not limited to stainlesssteel. In other variations, the device may be provided without a needle.In some variations, the needleless devices are intended to be attachedto a pre-existing needle (e.g., a lumbar puncture needle or a centralline catheter).

As shown in FIG. 1, the syringe 104 may further comprise a rigid needleshield 422. In some variations, the injection device 100 may comprise adeshielder configured to allow easy removal of the rigid needle shield422. In some variations, the deshielder or rigid needle shield 422 maycomprise an interlock to resist motion of the syringe 104 within thedistal housing 110 before removal of the rigid needle shield 422. Insome variations, the deshielder may be integrated with a cap 148 thatmay fit over the distal housing 110, as described in more detail above.In some variations, the rigid needle shield 422 may be asymmetric toresist rolling of the housing 102 when attached to the injection device100.

The syringe 104 may be configured to move longitudinally relative to thedistal housing 110 from a retracted position (shown in FIGS. 2A-2D and3A-3B) to an extended position (shown in FIGS. 2G-2N and 3E-3F). In aretracted position, the distal tip 424 of the needle 406 may be shieldedfrom exposure (e.g. the needle 406 may be protected from piercing orotherwise contacting tissue), and thus the distal tip 424 of the needle406 may be proximal to the distal end of the housing 102 (e.g., thedistal end 114 of the distal housing 110). The syringe 104 may be heldin a retracted position (i.e., it may resist distal motion relative tothe syringe 104) by a restraining element. In some variations, therestraining element may comprise one or more flexures 428, describedbelow. The syringe 104 may be moved toward an extended position by adistal force sufficient to overcome the resistance of the flexures 428,as described below. In an extended position, the distal tip 424 of theneedle 406 may be exposed (e.g., the distal tip 424 of the needle 406may be capable of piercing or other otherwise contacting tissue), andthus the distal tip 424 of the needle 406 may be distal to the distalend of the housing 102 (e.g., the distal end 114 of the distal housing110). When the syringe 104 is in an extended position, if the needleshroud 202 of the needle safety assembly 200 is in a retracted position,the distal tip 424 of the needle 406 may extend beyond the distal end ofthe distal housing 110 and the needle shroud 202 to pierce tissue to adesirable depth, as shown in FIGS. 2G-2L. In some variations, the distaltip 424 of the needle 406 may move about 6 mm to 8 mm, about 8 mm to 10mm, about 10 mm to 12 mm, or about 12 mm to 14 mm between retracted andextended positions. In some variations, the distal tip 424 of the needle406 may be about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm,about 6 mm, or about 7 mm proximal to the distal end 114 of the distalhousing 110 in a retracted position. In some variations, the distal tip424 of the needle 406 may be about 4 mm, about 5 mm, about 6 mm, about 7mm, about 8 mm, about 9 mm, or about 10 mm distal to the distal end 114of the distal housing 110 in an extended position.

FIG. 5 depicts an exploded perspective view of the injection device 100.In some variations, the injection device 100 may comprise a syringesleeve 430, as mentioned above, but need not. In these variations, thesyringe 104 may be slidably disposed with the syringe sleeve 430. Thesyringe sleeve 430 may comprise a distal portion 432 and a proximalportion 434. The distal portion 432 may be configured to fit slidablyaround the syringe body 402. The proximal portion 434 may have a largerdiameter (or maximum distance transverse to the longitudinal axis) thanthe distal portion 432, and may be configured to hold the power assembly106 in place, as described in more detail below. The syringe sleeve 430may be fixed relative to the distal housing 110, and may have alongitudinal axis aligned with the longitudinal axis of the housing 102.The syringe sleeve may comprise any suitable material, and in somevariations, the syringe sleeve 430 may comprise a deep drawn metal.

The distal portion 432 of the syringe sleeve 430 may also have attachedto it an interlocker 436. As shown in FIGS. 6A-6B, the interlocker 436may comprise a main body 438 that may be fixed within the proximalportion 434 of the syringe sleeve 430. The interlocker 436 may have aproximal opening 440, a distal opening 442, and a lumen 444therethrough. At least a portion of the ram 502 (described below) mayfit through the proximal opening 440 of the interlocker 436, and thesyringe body 402 of the syringe 104 may fit through the distal opening442 of the interlocker 436. The interlocker 436 may further comprise oneor more flexures 428 to resist distal movement of the syringe 104, and abiter interlock 448 to hold the biter 608 of the power assembly 106 inplace, both of which will be described in more detail below.

Returning to FIGS. 2A-2N, the ram 502 may be directly or indirectlyconnected to the proximal housing 108, such that movement of theproximal housing 108 can be transmitted to the ram 502. The ram 502 maybe configured to transmit distal force on the proximal housing 108 intodifferent motions, depending on the stage of the injection process. In afirst stage, distal force on the proximal housing 108 may be transmittedinto distal motion of the syringe 104 relative to the distal housing110. In a second stage, distal force on the proximal housing 108 may betransmitted into displacement of the contents of the reservoir 414 ofthe syringe 104 (e.g., a fluid or formulation comprising a therapeuticor diagnostic agent) through the lumen 408 of the needle 406.

In some variations, the ram 502 may be configured such that the effectsof distal force on the proximal housing 108 may occur in the orderdescribed above. That is, the ram 502 may be configured such that distalforce on the proximal housing 108 may be transmitted first into distalmotion of the syringe 104 relative to the distal housing 108, and thentransmitted second into displacement of the contents of the reservoir414 (e.g., a formulation comprising a therapeutic agent) through thelumen 408 of the needle 406. This may be desirable, for example, becauseit may allow the syringe 104 to move distally such that the needle 406may pierce a patient's tissue before the contents of the reservoir 414are displaced through the lumen 408 of the needle 406.

In some variations, the ordering of effects of distal force on theproximal housing 108 may be due to different amounts of force that arerequired for each motion. For example, the ram 502 may transmit distalforce on the proximal housing 108 into distal motion of the syringe 104relative to the distal housing 110 when the force on the proximalhousing 108 is above a first threshold (e.g., above about 1N, aboveabout 2N, above about 3N, above about 4N, above about 5N, above about6N, above about 7N, or higher); and the ram 502 may transmit distalforce on the proximal housing 108 into displacement of the contents ofthe reservoir 414 through the needle 406 when the force on the proximalhousing 108 is above a second higher threshold (e.g., above about 1N,above about 2N, above about 4N, above about 6N, above about 8N, aboveabout 10N, above about 12N, above about 14N, or higher). Thesethresholds may in some cases be desirable for other or additionalreasons. For example, it may be desirable that the force threshold toinitiate distal motion of the syringe be higher than the amount of forcerequired to insert the needle through the skin. It may also be desirablethat the force threshold to initiate distal motion of the syringe behigh enough to discourage accidental distal motion. Indeed, in somevariations, it may be desirable that the force threshold to initiatedistal motion of the syringe be high enough so as to force rapid needleinsertion. In some variations, the thresholds may be due to the proximalforces from friction on the syringe 104 and ram 502, respectively. Inother variations, the thresholds may be due to the proximal forces fromother sources on the syringe 104 and ram 502, respectively, such asproximal forces from a flexure or spring. In other variations, one ormore of the thresholds may be due to the proximal forces from frictionand other sources on the syringe 104, and ram 502, respectively. Itshould be appreciated that in some other variations, the ram 502 maytransmit distal force on the proximal housing 108 into different motionsin different orders and by different mechanisms. For example, in somevariations the effect of the distal force may be chosen by a mechanismfor manual selection by the user. In should also be appreciated that theram may have fewer or more motions into which it may transmit distalforce on the proximal housing 108.

As shown in FIGS. 2A-2N, the ram 502 may comprise a central portion 504and two arms 506 extending from opposite sides of the central portion504. The central portion 504 may be divided in a proximal centralportion comprising a connector rod 508, and a distal central portioncomprising a plunger 510. The two arms 506 may extend from the centralportion 504 at the dividing point 512 between the plunger 510 and theconnector rod 508. The connector rod 508 may be slidable within aportion of the actuation rod 636 (described in detail below), which mayin turn be fixedly attached to the end cap 118 of the proximal housing.However, in other variations (not shown), the connector rod may beconfigured to directly connect the ram to the proximal housing. In thosevariations, the connector rod may fit at least partially into areceiving cup on the inner surface of the end cap of the proximalhousing. The receiving cup may be located at the center of the end capand may be configured to hold the ram in a position aligned with thelongitudinal axis of the housing.

The plunger 510 may be configured to be slidable within the syringecavity 404 of the syringe 104. The distal end 516 of the plunger 510 maybe configured to engage with the seal 410 of the syringe 104. If theplunger 510 is moved distally relative to and within the syringe cavity404, the plunger 510 may push the seal 410 distally relative to andwithin the syringe cavity 404. This movement of the seal 410 maydecrease the volume of the reservoir 414 containing the formulationcomprising a therapeutic or diagnostic agent. Thus, distal motion of theplunger 510, and in turn of the seal 410, relative to and within thesyringe cavity 404 may cause the contents of the reservoir 414 to bedisplaced through the lumen 408 of the needle 406. The two arms 506 ofthe ram 502 may extend distally from opposite sides of the ram 502 fromits dividing point 512 along the central portion 504. The arms 506 maycomprise a proximal curved portion 518 and a distal straight portion520. The straight portion 520 of the arms 506 may be radially distancedfrom the plunger 510, such that if the plunger 510 is moved within thesyringe cavity 404, the straight portion 520 of the arms 506 may belocated outside of the syringe body 402. In some variations, the outersurface of the straight portion of the arms 506 may optionally comprisean indentation ridge for attachment of the indicator, as describedabove. The arms 506 may additionally be configured to attach to aportion of the power assembly 106 when the syringe 104 is in an extendedposition, as described below.

As shown in FIGS. 2E-2F, in the first stage of the injection process,distal force on the proximal housing 108 may be transmitted into distalmovement of the syringe 104 relative to the syringe sleeve 430 from aretracted position (shown in FIGS. 2C-2D) to an extended position (shownin FIGS. 2G-2H) if the distal housing 110 is held in place (e.g. bypressing the distal end 158 of the nose 116 of the distal housing 110against a patient's tissue) and if the distal force is above thenecessary force threshold. The threshold force required may be due tothe first pair of flexures 428, as described above. More specifically,when the threshold distal forced is reached, the flexures 428 maydeflect outward and over the proximal lip 452 of the syringe body 402,at which point the flexures 428 may no longer resist distal movement ofthe syringe 104. Distal force on the proximal housing 108 may then causedistal motion of the ram 502, which may in turn cause distal motion ofthe syringe 104, via the plunger 510 located within the syringe cavity404, toward the extended position. The syringe 104 may move distallywithin the syringe sleeve 430, which may move the needle 406 of thesyringe 104 distally toward the distal end of the nose 116 of the distalhousing 110. As the distal tip 424 of the needle 406 approaches thedistal end 158 of the nose 116 (shown in FIGS. 2E-2F), the needle shroud202 of the needle safety assembly 200 may be unlocked from a retractedposition, as described in detail above. As the distal tip 424 of theneedle 406 moves to extend beyond the distal end 158 of the nose 116,the needle 406 may pierce tissue pressed against the distal end 158 ofthe nose 116. The syringe 104 may continue to move distally relative tothe syringe sleeve 430 until the syringe 104 has reached an extendedposition (shown in FIGS. 2G-2H). At an extended position, the distal tip424 of the needle 406 may have reached the desired depth, as describedabove. The forward motion of the syringe 104 beyond the extendedposition may be limited by the proximal lip 452 contacting the distalend of the proximal portion 434 of the syringe sleeve 430. Because theproximal portion 434 of the syringe sleeve 430 may have a largerdiameter (or maximum distance transverse to the longitudinal axis) thanthe distal portion 432, as described above, the proximal lip 452 of thesyringe body 402 may fit within the proximal portion 434 but may not fitwithin the distal portion 432. In some variations, the injection device100 may comprise a cushioning element (e.g., a rubber or elastomerovermold on the interlocker 436 or other rubber or elastomer element)with which the proximal lip 452 may come into contact when it reachesits fully proximal position. Additionally or alternatively, theinjection device 100 may comprise a damping element, such as but notlimited to a rubber or elastomer seal on the outside surface of thesyringe body 402. In some variations, the injection device 100 maycomprise an insertion detent, which may cause the movement of the distaltip 424 of the needle 406 to occur at a specific rate, in order toachieve a desired insertion speed into tissue.

It should be noted that the syringe 104 may move distally with the ram502, rather than the ram 502 moving distally relative to the syringe 104(e.g., due to the plunger 510 moving distally relative to and within thesyringe cavity 404) in response to application of distal force on theproximal housing 108, due to the relative amounts of force required tomove the syringe 104 relative to the syringe sleeve 430 and to move theram 502 relative to the syringe 104, as described above, and due tomechanisms that may resist distal motion of the ram 502 relative to thesyringe 104. More specifically, the amount of force required to overcomethe first set of flexures 428 that may hold the syringe 104 in placerelative to the interlocker 436, as described above, may be less thanthe amount of force to overcome the rate control assembly 604 of thepower assembly 106 (described below) and/or the locking portion of theindicator that resists distal motion of the plunger 510 within thesyringe cavity 404 of the syringe 104, as described in more detailbelow. If the distal force on the proximal housing 108 is released whilethe syringe 104 is moving from a retracted position to an extendedposition, the syringe 104 may stay in place relative to the syringesleeve 430.

In the variation shown in FIGS. 2A-2N, distal motion of the plunger 510within the syringe cavity 404 may be resisted before the syringe 104 isin an extended configuration due to the locking portion of the indicator300, described above. Until the syringe 104 is in an extendedconfiguration, a protrusion 316 on the inner edge of locking portion 310may be mated with a recess 330 in the plunger 510, as shown in FIGS. 2A,2C, and 2E. Inward pressure on the outer tip of the locking portion 310from the inner surface of the interlocker 436 may resist radiallyoutward movement of the locking portion 310 out of the recess 330, thuskeeping the locking portion 310 and the plunger 510 mated. While mated,the indicator 300, the plunger 502, and the syringe 104 may be fixedrelative to each other and may move distally together as the syringe 104is moved toward an extended configuration. Once the syringe 104 is in anextended configuration, as shown in FIG. 2G, the locking portion 310 mayalign with the indicator recess 328 (described in more detail above).When distal force is applied to the plunger 510 via the proximal housing108, pressure on the inner edge of the locking portion 310 from theplunger 510 may push the locking portion 310 radially outward and intothe indicator recess 328. The locking portion 310 and the plunger 510may thus no longer be mated, allowing the plunger 510 to move distally.

After the syringe 104 has moved distally relative to the syringe sleeve430 such that the syringe 104 is in an extended position and the distaltip 424 of the needle 406 is at the desired depth, additional distalforce on the proximal housing 108 may be transmitted into distal motionof the ram 502 relative to the syringe cavity 404, if the force is abovethe necessary force threshold. When the force is above the necessaryforce threshold, the plunger 510 and seal 410 may be moved distallywithin the syringe cavity 404, as shown in FIGS. 2I-2J, which maydecrease the volume of the reservoir 414 and displace the contents ofthe reservoir 414 through the lumen 408 of the needle 406, as describedabove. Distal force on the proximal housing 108 may continue to causethe contents of the reservoir 414 to be displaced through the lumen 408of needle 408 until the seal 410 has traveled to the distal end 462 ofthe syringe cavity 404 (shown in FIGS. 2K-2L), at which time the fulldosage of the therapeutic or diagnostic agent may have been injectedinto the patient. In some variations, the total displacement of theplunger 510 during distal motion of the ram 502 relative to the syringecavity 404 may be about 20 mm to 25 mm, about 25 mm to 30 mm, about 30mm to 35 mm, about 35 mm to 40 mm, about 40 mm to 45 mm, about 45 mm to50 mm, about 50 mm to 55 mm, about 55 mm to 60 mm, about 60 mm to 65 mm,about 65 mm to 70 mm, or about 70 mm to 75 mm. In some variations, thethreshold force required to move the plunger 510 and seal 410 distallywithin the syringe cavity 404, once the locking portion 310 and theplunger 510 are no longer mated, may be due to the rate control assembly604 of the power assembly 106, as described below.

The power assembly may comprise a stored energy source and a ratecontrol assembly. The stored energy source may be configured to provideforce to displace the contents of reservoir of the syringe. In somevariations, the stored energy source may be configured to do so bycontributing to the distal motion of the plunger or seal within thesyringe cavity. In some variations, the power assembly may allow a user(a patient or another person) to direct the injection process in anintuitive way by directing the injection by pressing the injectiondevice against a patient's skin, but the power assembly may supplyadditional supplemental injection force, such that the user does notneed to provide the full force needed to carry out the injection. Inaddition, the power assembly may in some variations assist withproviding a desirable user experience. This may include smoothoperation, particularly when transitioning between static, slow, andfast injection states. While in the injection device 100 the powerassembly supplies an injection force supplemental to the user-suppliedinjection force, it should be appreciated that in other embodiments, thepower assembly may supply the full injection force. It should also beappreciated that in some variations, injection device may not provide asupplemental injection force.

The injection force provided by the power assembly may thus besufficient (alone or in addition to injection force supplied by theuser) to inject a given volume of a given formulation through a givensize needle in a given time. In some variations, for example, the powerassembly may be capable of 2 mL of 19 cP solution in 10 seconds througha 27 gauge thin-wall needle 17 mm in length. In some variations, thepower assembly may provide supplementary injection forces of up to about5N, about 10N, about 15N, about 20N, about 25N, about 30N, about 35N,about 40N, about 45N, about 50N, about 55N, about 60N, about 65N, about70N, about 75N, about 80N, about 85,or about 90N at the beginning of theinjection.

In some variations, it may be desirable for the power assembly todeliver a substantially constant force for the duration of theinjection. In some variations, a substantially constant force for theduration of the injection may be achieved, for example, using a longspring with a low spring rate. In some of these variations, the springfade may be about 5-10%, about 10-15%, about 15-20%, about 20-25%, about25-30%, about 30-35%, or about 35-40% over the course of the injection.In other variations, a substantially constant force for the duration ofthe injection may be achieved, for example, with a spring having ashorter total length by mounting an extension spring to a compressionspring (as described in more detail with respect to the embodiment ofthe injection device shown in FIG. 10). In other embodiments, asubstantially constant force for the duration of the injection may beachieved, for example, with a pressure from a liquid propellant in asupercritical state (as described in more detail with respect to theembodiment of the injection device shown in FIG. 18). In some othervariations, the power assembly may provide a varying force for theduration of the injection.

In some variations, the rate control assembly may comprise a brakingassembly that may limit or restrict the stored energy source fromcontributing to the displacement of the contents of the reservoir of thesyringe. In some variations, the rate control assembly may be configuredto do so by limiting or restricting the distal movement of a plunger orseal within the syringe cavity.

FIG. 7 depicts a perspective view of an example of the stored energysource 602 of the injection device 100. The stored energy source 602 maycomprise a compression spring 606. The compression spring 606 may bedirectly or indirectly attached or in contact with a first surface fixedrelative to the distal housing 110 on one end, and may be directly orindirectly attached or in contact with the a second surface fixedrelative to the plunger 510 of the ram 502 on the other end. Thus, theforce from the compression spring 606 on the first and second surfacesmay bias the first and second surfaces away from each other, which mayin turn bias the plunger 601 distally relative to the syringe cavity404. More specifically, the compression spring 606 may be sized to fitwithin the distal housing 110 and around the proximal portion 434 of thesyringe sleeve 430. The compression spring 606 may be housed by a springsleeve 610, but need not be. In variations having a spring sleeve 610,the spring sleeve 610 may be substantially cylindrical and configured tofit around the compression spring 606. The spring sleeve 610 may bemoveable relative to the syringe sleeve 430, and may have an inwardlyextending distal lip 612. The distal end 616 of the compression spring606 may be attached or connected to the distal lip 612. The proximal end614 of the compression spring 606 may be attached or connected to aninwardly extending proximal lip 454 on the proximal portion 432 of thesyringe sleeve 430, which may in turn be fixed relative to the distalhousing 110, as described above.

The force from the compression spring 606 against the distal lip 612 ofthe spring sleeve 610 may be transmitted into distal motion of the ram502 by a biter 608, as shown in FIGS. 8A-8B. Alternatively, in somevariations not having a syringe sleeve, the compression spring may pressdirectly against the biter. As shown in FIGS. 8A-8B, the biter 608 maycomprise a main body 618. The main body 618 may be configured to fitwithin the distal housing 110 and may have a lumen 626 therethrough. Thebiter 608 may comprise one or more inner projections 628 extendinginward into the lumen 626, described in more detail below. In somevariations, the biter 608 may comprise two attachment ports 622, whichmay be configured to engage with the distal ends 538 of the straightportions 520 of the arms 506 of the ram 502 when the syringe 104 reachesan extended position, as shown in FIG. 2H. In some variations, thedistal ends 538 of the ram 502 may engage with the attachment ports 622by deflecting radially outward as the distal ends 538 come into contactwith the attachment ports 622 as the ram 502 moves distally, and thensnapping into place onto the attachment ports 622. The engagementbetween the attachment ports 622 and the distal ends 538 is such thatthe biter 608 may rotate relative to ram 502, as described in moredetail below.

As shown in FIG. 7, the lumen 626 of the biter 608 may be configured tofit slidably around the distal portion 432 of the syringe sleeve 430.While the lumen 626 is shown as having a substantially circularcross-section, it should be appreciated that the lumen 626 may have anysuitable shape (e.g., having an elliptical cross-section, oblongcross-section, ovoid cross-section, square cross-section, rectangularcross-section, triangular cross-section, etc.), depending in part on thecross-section of the syringe 104 and/or syringe sleeve 430. As shown inFIG. 7, the distal lip 612 of the spring sleeve 610 may press distallyagainst the proximal projection 620 of the biter 608. The compressionspring 606 may therefore bias the biter 608 distally away from theproximal end 614 of the spring sleeve 610. This may in turn bias thearms 506 of the ram 502 distally away from the proximal end 614 of thespring sleeve 610, which may bias the plunger 510 of the ram 502distally relative to the syringe sleeve 430 and within the syringecavity 404.

The compression spring 606 may be made of any suitable material, such asbut not limited to music wire, stainless steel, and spring steel. Thespring rate of the compression spring 606 may be chosen to deliver anappropriate force based on the formulation viscosity, needle choice,volume, and desired injection time, as described above. In somevariations, for example, the compression spring 606 may be configured todeliver a force of up to about 5N, about 10N, about 15N, about 20N,about 25N, about 30N, about 35N, about 40N, about 45N, about 50N, about55N, about 60N, about 65N, about 70N, about 75N, about 80N, about 85,orabout 90N when the compression spring 606 initially begins to expand.FIG. 21 show an illustrative graph of the user force required to performan injection using an injection device having a power assembly similarto the power assembly 106 of the injection device 100, illustrating theinitial actuation force and relatively stable spring fade. The graphrepresents a liquid having a viscosity of approximately 9 cP injectedthrough a 27 gauge, thin-wall needle, with the seal displacing thecontents of the reservoir at approximately 6 mm/s, which generallyrequires approximately 15N of force. However, as seen in the graph,approximately 4 to 6N of user force was required, thus representing aload multiplication factor around 3. It should be noted that this graphis merely illustrative of the force requirements for a similar device,and is not meant to indicate that the injection device 100 may or mustconform to this representation.

As described above, the rate control assembly of the power assembly mayat times comprise a braking assembly that may slow, limit, or restrictthe stored energy source from providing force to displace the contentsof the reservoir of the syringe. In some variations, the rate controlassembly may be moveable between a closed configuration and an openconfiguration. When the rate control assembly is in a closedconfiguration, the rate control assembly may stop or reduce thedisplacement of the contents of the reservoir of the syringe. When therate control assembly is in an open configuration, the rate controlassembly may not limit or restrict the displacement of the contents ofthe reservoir of the syringe. In some variations, the rate controlassembly may be configured to limit or restrict the displacement of thecontents of the reservoir of the syringe by limiting or restricting thedistal motion of a plunger within the syringe cavity when in a closedconfiguration. When in an open configuration, the rate control assemblymay not limit or restrict the distal motion of a plunger within thesyringe cavity, thus allowing the stored energy source to act upon theplunger to move it distally relative to and within the syringe cavity,which may move the seal of the syringe distally within the syringecavity to displace the contents of the reservoir through the lumen ofthe needle.

The rate control assembly may be a braking assembly. In some variations,force generated by the rate control assembly and/or another component ofthe injection device 100 may counteract or partially or fully oppose theforce from the stored energy source. In some variations, the brakingassembly may be friction-based. That is, when the rate control assemblyis in a closed configuration, friction between the rate control assemblyand another component of the injection device 100 may counteract orpartially or fully oppose the force from the stored energy source. Insome variations, the force when the rate control element is in a closedconfiguration (e.g., friction between the rate control assembly in aclosed configuration and another component of the injection device 100)may counteract or oppose the force from the stored energy sourcecompletely, resisting distal movement of the plunger 510 within thesyringe cavity 404 of the syringe 104. In other variations, the force(e.g., friction between the rate control assembly in a closedconfiguration and another component of the injection device) maypartially counteract or oppose the force from the stored energy source,damping the distal movement of the plunger within the syringe cavity dueto the stored energy source. In some variations, when the rate controlassembly is in an open configuration, there may not be a force (e.g.,friction between the rate control assembly and another component of theinjection device 100) opposing the stored energy source, which may allowthe stored energy source to cause the plunger 510 to be moved distallywithin the syringe cavity 404 of the syringe 104. In other variations,there may be a force (e.g., friction between the rate control assemblyand another component of the injection device 100) opposing the storedenergy source, but the force may be less than is required to fullyresist the stored energy source from acting on the plunger 510.

As shown in FIG. 9, the rate control assembly 604 may comprise the biter608 discussed above. The biter 608 may be reversibly and selectivelymoved between open and closed configurations. When the biter 608 is in aclosed configuration, friction between the biter 608 and the syringesleeve 430 may counteract or partially or fully oppose the distal forcefrom the compression spring 606. The friction may be due to contactbetween the inner projections 628 of the biter 608 and the syringesleeve 430. The inner projections 628 may be configured such that whenthe biter 608 is tipped such that the longitudinal axis 630 through thelumen 626 is displaced from the longitudinal axis 144 of the housing 102(and thus displaced from the longitudinal axis 470 of the syringe sleeve430), the inner projections 628 come into contact with the syringesleeve 430 with a force sufficient to create enough friction tocounteract or partially or fully oppose the distal force from thecompression spring 606. While FIGS. 8A-8B show the biter 608 ascomprising three inner projections 628 approximately equally spacedaround the circumference of the lumen 626, it should be appreciated thatin other variations, the biter may comprise other numbers of innerprojections and/or arrangements. For example, in some variations, thebiter may comprise two or four inner projections equally spaced aroundthe circumference of the lumen.

When the biter 608 is in an open configuration, the longitudinal axis630 through the lumen 626 of the main body 618 of the biter 608 may berotated from the open configuration toward a position parallel to thelongitudinal axis 144 of the housing 102 (and thus toward a positionparallel to the longitudinal axis 470 of the syringe sleeve 430). Whilein some cases the biter 608 may rotate such that the longitudinal axis630 may be parallel to the longitudinal axis 144 of the housing, thelongitudinal axis 630 need not rotate so far as to be parallel to thelongitudinal axis 144 in order to be in an open configuration. Oncerotated into an open configuration, the inner projections 628 may not bein contact with the syringe sleeve 430. Thus, there may not be frictionbetween the biter 608 and the syringe sleeve 430. In some variations,the biter 608 may also, but need not, have an intermediate configuration(not shown), wherein there is friction between the biter 608 and thesyringe sleeve 430, but the friction between the biter 608 and thesyringe sleeve 430 may be less than the distal force from thecompression spring 606. It should be appreciated that some variations ofthe injection devices described here may not have a syringe sleeve, andin those variations, when the biter is in a closed configuration, theremay be friction between the inner projections 628 and the outer surface512 of the syringe body 402. While the force in the embodiment shown inFIG. 9 is due to friction, it should also be appreciated that in othervariations the force may be due to another form of interaction betweenthe braking assembly and another component of the injection device. Forexample, in some variations, a biter may comprise one or more features(e.g., ridges or teeth) that are configured to mechanically interact orinterface with one or more features of a syringe sleeve (e.g., ridges orteeth), which may generate a force that may partially or fully opposethe force from the stored energy source.

In some variations, the rate control assembly 604 may be biased toward aclosed configuration, such as by a distal force on the biter 608 thatacts radially asymmetrically on the biter 608. In the power assembly106, the biter 608 may be biased toward a closed configuration by thecompression spring 606. The force from the compression spring 606biasing the distal lip 612 of the spring sleeve 610 away from theproximal lip 454 of the syringe sleeve 430 may cause the distal lip 612of the spring sleeve 610 to push distally against the proximalprojection 620 of the biter 608, as described above. The proximalprojection 620 of the biter 608 may extend around less than 180 degreesof the main body 618 of the biter 608 on a first side 632, and thereforethe distal force on the proximal projection 620 of the biter 608 fromthe distal lip 612 of the spring sleeve 610 may cause the biter 608 totilt such that the first side 632 may move distally relative to theother second side 634 of the biter 608. The longitudinal axis 630through the lumen 626 of the biter 608 may thus be rotated relative tothe longitudinal axis 144 of the housing 102. This may cause the biter608 to move into a closed configuration and the inner projections 628 ofthe biter 608 to contact the syringe sleeve 430, as described above. Itshould be appreciated that while in the embodiment of the biter 608shown in FIGS. 8A-8B the proximal projection 620 extends approximately40 degrees around the main body 618 of the biter 608 and isapproximately 8 mm in width, in other embodiments, the proximalprojection 620 may extend less or more around the biter 608 (e.g., about10 degrees, about 20 degrees, about 40 degrees, about 60 degrees, about80 degrees).

The rate control assembly 604 may further have, in addition to open andclosed configurations, an inactivated configuration (shown in FIG. 7).In the inactivated configuration, the biter 608 may be held by theinterlocker 436, such that it resists movement relative to theinterlocker 436. The interlocker 436 may comprise a biter interlock 448,which may comprise a tab 466 that may extend inwardly from the distalend of the biter interlock 448. The tab 466 may be configured to matewith a projection 676 of the biter 608. When the tab 466 is mated withthe projection 676, the biter interlock 448 may resist motion of thebiter 608 relative to the interlocker 436. As shown in FIG. 8A, theprojection 676 may comprise a U-shaped hook, through which the tab 466may attach, as shown in FIG. 7. The tab 466 may resist distal motion ofthe projection 676, and in turn of the biter 608 relative to theinterlocker 436. The rate control assembly 604 may be released from theinactivated configuration by distal movement of the syringe 104. In thevariation shown in FIG. 7, the biter 608 may be released from theinterlocker 436 by the proximal lip 452 of the syringe body 402. As theproximal lip 452 moves distally relative to the interlocker 436 as thesyringe 104 moves toward an extended configuration, the proximal lip 452may press against the tab 466 of the biter interlock 448, pushing itradially outward. When the tab 466 is pushed radially outward, it maymove outward through the opening in the U-shaped hook of projection 676and may disengage from the projection 676. The biter 608 may thus nolonger be held in place by interlocker 436. While the variation shown inFIG. 7 comprises two biter interlocks 448 configured to mate with twoprojections 676, it should be appreciated that in other variations, theinterlocker 436 may comprise fewer (e.g., zero or one) or more (e.g.,three, four, five, or more) biter interlocks and/or projections.

The biter 608 may be moved into an open configuration by rotating thebiter 608 such that the longitudinal axis 630 through the lumen 626 ofthe main body 618 of the biter 608 is moved toward a position parallelto the longitudinal axis 144 of the housing 102 (and thus toward aposition parallel to the longitudinal axis 470 of the syringe sleeve430). As described above, while in some cases the biter 608 may rotatesuch that the longitudinal axis 630 may be parallel to the longitudinalaxis 144 of the housing, the longitudinal axis 630 need not rotate sofar as to be parallel to the longitudinal axis 144 in order to be in anopen configuration. In some variations, the biter 608 may be moved froma closed configuration to an open configuration by application of adistal force on second side 634 of the biter 608. Such a distal forcemay counterbalance or partially or fully oppose the distal force on theproximal projection 620 of the biter 608 from the distal lip 612 of thespring sleeve 610. FIG. 9 shows one example of an actuation rod 636 thatmay apply this distal force. The actuation rod 636 may be selectivelyand reversibly moved between an advanced position, during which it mayengage the biter 608 at a contact point 642 on the second side 634 tourge it toward an open configuration, and a withdrawn position, duringwhich it may not engage the biter 608, thus leaving the biter 608 in aclosed configuration. The distal end 644 of the actuation rod 636 may beconfigured to engage the second side 634 of the biter 608 at the contactpoint 642. In some variations, the contact point 642 may optionallycomprise a concave region to assist in alignment of the actuation rod636 and biter 608. In some variations, the distal end 644 of theactuation rod 636 may optionally have one or more features to promoteengagement with the contact point 642 of the biter 608.When theactuation rod 636 presses on the biter 608 at the contact point 642, theactuation rod 636 may tilt the biter 608 into an open configuration(described above). This may occur when the distal end 644 of theactuation rod 636 presses down on the contact point 642 with sufficientforce to counteract or partially or fully oppose the force from thecompression spring 606 on the proximal projection of the biter 608.

When the syringe 104 is in an extended position (described above), theactuation rod 636 may be selectively and reversibly moved betweenadvanced and withdrawn positions by applying distal force to theproximal housing 108. When distal force is applied to the proximalhousing 108 while the distal housing 110 is held in place (e.g., bypressing the distal end 158 of the nose 116 of the distal housing 110against a patient's tissue) and the syringe 104 is in an extendedposition, the proximal housing 108 and the actuation rod 636 may bemoved distally relative to the biter 608. The force on the contact point642 of the biter 608 from the distal end 644 of the actuation rod 636may move the biter 608 into an open configuration as described above.When the biter 608 is in an open configuration, the distal force appliedto the distal end of the housing and the distal force from thecompression spring 606 may both act to urge the biter 608 distally. Thisin turn may urge the plunger 510 distally via the arms 506 of the ram502, which in turn may urge the seal 410 distally to displace thecontents of the reservoir 414 through the lumen 408 of the needle 406,as described above.

In some variations, the actuation rod 636 may be moveable betweenadvanced and withdrawn positions relative to the biter 608 by distalforce on the proximal housing 108 because the relative locations of theram 502 and the actuation rod 636 may be variable. In some variations,the actuation rod 636 may comprise an elongate rod 638 having a proximalend 640 that is fixedly attached to the proximal housing 108. While theactuation rod 636 is shown in FIG. 9 as attaching to the inner surface186 of end cap 118 of proximal housing 108, it should be appreciatedthat in other variations the actuation rod 636 may be fixed to theproximal housing 108 at other locations and via other methods, or inother variations may be integral to the proximal housing 108. Incontrast, the ram 502 may have extended and retracted positions relativeto the actuation rod 636 and/or to the proximal housing 108. In onevariation, the connector rod 508 of the ram may fit within a bore 646 inthe actuation rod 636, being slidable between an extended position and aretracted position within the bore 646. In another variation (notshown), the proximal end of the ram may be slidable between an extendedposition and a retracted position within a receiving cup on the insideof the end cap. In some variations, the ram 502 may be biased toward anextended position relative to the proximal end of the proximal housing108. The biasing may be due to a compression spring 526. Morespecifically, the compression spring 526 may fit slidably around theconnector rod 508 of the ram 502. The ram 502 may be biased toward anextended position relative to the actuation rod 636 by the compressionspring 526, which may fit slidably around the connector rod 508 betweenthe plunger 510 and the actuation rod 636. In other variations (notshown) in which the ram is connected to the end cap directly, theproximal end of the compression spring may be in contact with orattached to a portion of the end cap and the distal end of thecompression spring may be in contact with a portion of the ram. Thus,the compression spring 526 may bias the ram 502 and the proximal housing108 away from each other, thus biasing the ram 502 toward an extendedposition. It should be appreciated that the compression spring 526 maybe at other locations in order to bias the ram 502 and the proximalhousing 108 away from each other.

Thus, when the syringe 104 is in an extended position (described above),the actuation rod 636 may be selectively and reversibly moved betweenadvanced and withdrawn positions by applying distal force to theproximal housing 108, which may move the ram 502 from an extended to aretracted position relative to the actuation rod 636.

If the distal force on the proximal housing 108 is released, the bias ofthe ram 502 toward an extended configuration relative to the actuationrod 636 due to the compression spring 526 may cause the proximal housing108 and actuation rod 636 to move distally away from the ram 502.However, the syringe 104 may stay in place relative to the syringesleeve 430, and the ram 502 may stay in place relative to the syringe104. As such, the actuation rod 636 may be moved from an advancedposition to a withdrawn position, to move distally away from the biter608 such that it no longer contacts the biter 608 at the contact point642. Removing the application of distal force at the contact point 642may cause the biter 608 to return to a closed configuration, asdescribed above. This may allow the user to selectively and reversiblystart and stop, or increase or decrease the speed of, the injectionprocess.

In some variations, but not wishing to be bound by such a theory, theamount of distal force that may be applied to the second side of the abiter having a similar design to the biter 608, in order to move thebiter from a closed configuration to an open configuration, may bemathematically described in a two-dimensional model as

$U = \frac{S\left( {e + \frac{d}{2} - \frac{b}{2\mu}} \right)}{\frac{d}{2} + \frac{b}{2\mu} + g}$

where U is the distal force applied, S is the force from the compressionspring on the biter, μ is the coefficient of friction between thesyringe sleeve and the biter, and e, g, d, t, and G represent thedistances illustrated schematically in FIG. 24A. In a model having threepoints of contact between the biter and the syringe sleeve, the amountof distal force that may be applied to the second side of a biter tomove it from a closed configuration to an open configuration maysimilarly be mathematically described as

$U = \frac{S\left( {e + \frac{d}{1 + {\cos \; \theta}} - \frac{b}{\left( {1 + {\sec \; \theta}} \right)*\mu}} \right)}{d - \frac{d}{1 + {\cos \; \theta}} + \frac{b}{\left( {1 + {\sec \; \theta}} \right)*\mu} + g}$

where θ represents the angle of the points of contact, as illustratedschematically in FIG. 24B. It should of course be appreciated that theseequations describe highly simplified models and may not represent theactual force required the move the biter 608 described here from aclosed to an open configuration.

In some variations, the injection device 100 may comprise anautocomplete mechanism, which may cause the full volume of the reservoir414 to be automatically displaced through the lumen 408 of the needle406 within a certain tolerance of the total injection (e.g., withinabout 85% of the injection, within about 90% of the injection, withinabout 95% of the injection, or more, or within about 1 mm of fulldisplacement, about 2 mm of full displacement, about 3 mm of fulldisplacement, or about 4 mm of full displacement, etc.), regardless of auser's application of distal force to the proximal housing 108. In somevariations, autocompletion may be caused by the biter 608 and syringesleeve 430 no longer generating a frictional force once the biter 608moves to a particular distal point along the distal portion 434 of thesyringe sleeve. For example, the distal portion 434 of the syringesleeve 430 may comprise a region near its distal end having a smallerdiameter (or maximum distance transverse to the longitudinal axis)smaller than the remainder of the distal portion 434 of the syringesleeve 430, such that when the biter 608 moves distally to reach thisregion, the biter 608 may no longer contact the syringe sleeve 430.Thus, there may be no friction between the biter 608 and the syringesleeve 430, and thus no force opposing the distal force from thecompression spring 606. As a result, the dose may autocomplete. Asanother example, instead of the full diameter of the distal portion 434being smaller in a region near its distal end, the distal portion 434 ofthe syringe sleeve 430 may comprise inward notches at the locations atwhich the biter 608 would contact the syringe sleeve 430 (e.g. at thelocations of inner projections 628), which may eliminate or reduce thefriction between the biter 680 and syringe sleeve 430 to causeautocompletion.

In some variations, one or more of the elements of injection device 100may optionally comprise clocking features to correctly orient theelements relative to each other. In some variations, elements of theinjection device 100 may comprise longitudinal ribs and grooves (e.g.,narrow grooves molded onto the interior of the proximal housing 108 andshort mating ribs on the exterior of distal housing 110) that may engageto provide alignment, and may also resist rotation of the elementsrelative to each other once engaged. In some variations, elements of theinjection device 100 may comprise one or more (e.g., two, three, four,five, or more) teeth on a first element and a corresponding one or more(e.g., two, three, four, five, or more) slots in a second element,wherein the teeth and slots are configured to engage when the first andsecond slots are properly aligned.

Another embodiment of an injection device 700 is depicted in FIGS. 10,11A-11B, and 12A-12F, comprising a housing 702, a syringe 704, and apower assembly 706. The housing 702 may be similar to the housing 102described above with respect to injection device 100, and may have thesame components, configurations, and functions. As shown in FIG. 10,however, the proximal housing 708 and distal housing 710 may have anelliptical cross-section, which may accommodate the power assembly 706,described below. An elliptical shape may also have certain benefits,including having an ergonomic form, allowing the contents of the syringeto be easily viewed, and resisting rolling of the device when beinghandled or stored. In some variations, the minor axis of thecross-section of the housing 702 may be less than or equal to about 20mm, about 25 mm, about 30 mm, about 35 mm, or about 40 mm. Additionallyor alternatively, in some variations, the viewing region 724 maycomprise an opening 760 in the distal housing 110, which may have arounded rectangular shape.

In some variations, the housing 702 may optionally further comprise acap 772, which may be similar to the cap 148 described above withrespect to injection device 100, and may have the same components andfunctions as described above. FIGS. 11A-11B show side views of theinjection device 700 with a cap 772 attached and removed, respectively.The cap 772 may comprise a viewing region 774, which may coincide withthe viewing region 724 of the distal housing when the cap 772 isattached to the remainder of the housing 702.

FIGS. 12A-12F depict longitudinal cross-sectional views of the injectiondevice 700 in various stages during use. FIG. 12A depicts the devicebefore use. FIG. 12B depicts the device with the rigid needle shield andcap removed. FIG. 12C depicts the device with the syringe in an extendedposition. FIG. 12D depicts the device with the plunger moved to thedistal position within the syringe cavity. FIG. 12E depicts the devicewith the end-of-dose indicator in an activated configuration. FIG. 12Fdepicts the device with the needle shroud extended. FIGS. 13A-13C showlongitudinal cross-sectional views of a distal portion of the injectiondevice 700, showing a needle shield assembly. Like the injection device100, the injection device 700 may comprise a needle safety assembly 800that may be movable between a retracted position (shown in FIGS.13A-13B) and an extended position (shown in FIGS. 13C-13D), as describedin detail above with regard to needle safety assembly 200. As shown inFIGS. 13A-13D the needle safety assembly 800 may comprise an extendableneedle shroud 802, a biasing element 818, and a locking assembly 826,having the same components, positions, and functions as described abovewith respect to needle safety assembly 800. However, with regard to thebiasing element, the biasing element 818 may comprise a compressionspring 820, which may have a cylindrical shape and may fit within thelumen 808 of the needle shroud 802. The proximal end 822 of thecompression spring 820 may contact a ledge 776 extending radiallyoutward from the inner sheath 762 of the nose 716, and the distal end824 of the compression spring 820 may contact a lip 816 extendingradially inward from the needle shroud 802. While the lip 816 is shownas located at the distal end 812 of needle shroud 802 in FIGS. 13A-13D,it should be appreciated that in other variations a lip may extend froma location proximal to the distal end 812 of the needle shroud 802. Insome variations, the proximal end 822 of the compression spring 820 maybe fixedly attached to the inner sheath 762 of nose 716, but it need notbe (e.g., the compression spring may rest against the nose 716 but maybe unattached). It should also be appreciated that in other variations,the proximal end 822 of the compression spring 820 may contact or befixedly attached a portion of the distal housing 710.

In some variations, locking assembly 826 of the needle safety assembly800 of injection device 700 may, like the locking assembly 226 ofinjection device 100, hold the needle shroud 802 in a retracted positionand/or in an extended position. In some variations, the locking assembly826 may comprise one or more latches 828, which may have the samecomponents, positions, and functions as described above with respect tothe injection device 100. However, in some variations, the latches 828may be configured to mate with a portion of the nose 716, such that whenmated, the latches 828 resist motion of the needle shroud 802 relativeto the distal housing 710. As shown in FIGS. 13A-13D, the nose 716 maycomprise an inner sheath 762 comprising four proximal slots 764. Thefour proximal slots 764 may be located on the inner sheath 762 such thatwhen the tabs 834 of the latches 828 are mated with the proximal slots764, the needle shroud 802 may be located in a retracted position. Whenthe tabs 834 are mated with the proximal slots 764, the elongate portion830 of the latches 828 may be flush against the outer surface 958 of thesyringe sleeve 930 (described below), while the tabs 834 of the latches828 may be inserted radially into the proximal slots 764. The lockingassembly 826 may resist distal motion due to a biasing force from thebiasing element 818 because of the proximally oriented force applied tothe distal surface of the tabs 834 by the distal surface of the proximalslots 764.

The locking assembly 826 may be configured such that the needle shroud802 may be unlocked from a retracted position (e.g., the lockingassembly 826 may no longer hold the needle shroud 802 in a retractedposition) by distal motion of the syringe 704. In some variations, thetabs 834 may be configured such that they can be released from theproximal slots 764 by distal movement of the syringe body 902 of thesyringe 704 relative to the nose 716. For example, in the variationshown in FIGS. 13A-13D, the tabs 834 may have a triangular, proximallytapering shape. Thus, as the syringe body 902 of the syringe 704 ismoved distally relative to the nose 716 and within the inner sheath 762,the distal end of the syringe body 902 may engage the inner surface ofthe tabs 834 protruding through the proximal slots 764. As the syringebody 902 of the syringe 704 continues to slide distally along the innersurface of the inner sheath 762 of the nose 716, the outer surface ofthe syringe body 902 gradually pushes the tabs 834 further radially outof the proximal slots 764. Once the outer surface of the syringe body902 has fully pushed the tabs 834 radially out of the proximal slots764, the tabs 834 may no longer be mated with the proximal slots 764 andmay no longer resist distal motion of the needle shroud 802 relative tothe distal housing 710. Like the needle shroud 202 of the injectiondevice 100, when the needle shroud 802 of the injection device 700 isunlocked from a retracted position, it may move to an extended positionif an appropriate force is applied, or such a force may be partially orfully counterbalanced by an opposing force, as described in detail abovewith regard to the needle shroud 202. Likewise, the needle shroud 802 ofthe injection device 700 may be unlocked from a retracted position justbefore the distal tip 924 of the needle 906 of the syringe 704 extendsfrom the distal end 758 of the nose 716, as described in detail abovewith regard to the needle shroud 202.

Similarly, the needle shroud 802 of the injection device 700 mayadditionally or alternatively be configured to be locked in an extendedposition once moved to an extended position, as described in detail withregard to the needle shroud 202. However, in the variations shown inFIGS. 13A-13D, the inner sheath 762 of the nose 716 may comprise fourdistal slots 770 configured to mate with the tabs 834 of the latches 828of the locking assembly 826. As shown in FIGS. 13C-13D, the distal slots770 may be located on the inner sheath 762 to coincide with the positionof the tabs 834 when the needle shroud 802 is in an extended position.When the needle shroud 802 moves into an extended position, the tabs 834on the latches 828 may mate with the distal slots 770. When the tabs 834on the latches 828 are mated with the distal slots 770, the lockingassembly 826 may resist motion of the needle shroud 802 relative to thenose 716.

The housing 702 may also comprise an indicator that, like the indicatorsdescribed with respect to the injection device 100, may indicate theprogress or completion of the injection, as described in detail above,and may have activated and inactivated configurations. FIGS. 14A-14B arelongitudinal cross-sectional views and elevational side views,respectively, of a proximal portion of the injection device 700 showingan end-of-dose indicator 900 having a different visual appearanceassociated with the activated and inactivated configurations ininactivated and activated configurations. In the variation shown inFIGS. 14A-14B, the indicator 900 may comprise the ram crossbar 1112 ofthe ram 1102, described in greater detail below. The ram crossbar 1112may be configured such that when the proximal surface 1118 of the ramcrossbar 1112 is adjacent to the inner surface 768 of the end cap 718 ofthe proximal housing 708, at least a portion of the ram crossbar 1112may be seen from outside the end cap 718. In some variations, at least aportion of the ram crossbar 1112 may have a color or pigment that may becapable of being more easily noticed, such as but not limited to red,yellow, orange, green, magenta, blue, and the like. In order for the ramcrossbar 1112 to be seen through at least a portion of end cap 718, insome variations, at least a portion of the end cap 718 may betranslucent or transparent. In variations in which at least a portion ofthe end cap 718 is translucent, the level of translucency may be suchthat the coloring of the ram crossbar 1112 may be perceived through theend cap 718 when the ram crossbar 1112 is adjacent to the viewingportion.

The indicator 900 may further comprise a biasing element 920, which maybe configured to bias the indicator 900 toward an inactivatedconfiguration. As shown in FIGS. 14A-14B, in some variations, thebiasing element 920 may comprise a locking spring 1246, described ingreater detail later with respect to the power assembly 706 of injectiondevice 700. The proximal end 1258 of the locking spring 1246 may beattached or in contact with the inner surface 768 of the end cap 718 ofthe proximal housing 708, while the distal end 1256 of the lockingspring 1246 may be attached to or in contact with a portion of the ram1102, as described in greater detail later. The locking spring 1246 maythus bias the ram crossbar 1112 away from the inner surface 768 of theend cap 718 of the proximal housing 708. The bias of the ram crossbar1112 away from the inner surface 768 of the end cap 718 may be overcomeby distal force on the proximal housing 708 at the completion of thefull injection of the contents of the reservoir 914, when the plunger1110 has traveled the full length of the syringe cavity 904, asdescribed in more detail below.

The syringe 704 of the injection device 700 may be similar to thesyringe 104 described above with respect to injection device 100, andmay have the same components, positions, and functions as describedabove. The injection device 700 may further comprise a syringe sleeve930. FIG. 15 depicts a perspective view of a syringe 704 and syringesleeve 930 of the injection device 700. The syringe sleeve 930 mayattach the syringe body 902 of the syringe 704 to the ram interlock 1226(described in more detail below). The proximal lip 952 of the syringebody 902 may rest on the proximal lip 954 of the syringe sleeve 930. Theproximal lip 954 of the syringe sleeve 930 may comprise four latches964, which may be configured to attach to four corresponding recesses onthe distal side of the ram interlock 1226 (described below). Thus, whenthe syringe sleeve 930 is attached to the ram interlock 1226, theproximal lip 952 of the syringe body 902 may be fixed between theproximal lip 954 of the syringe sleeve 930 and the ram interlock 1226,causing the syringe body 902 to resist distal motion relative to thesyringe sleeve 930. The syringe sleeve may comprise any suitablematerial or materials, but in some variations, the syringe sleeve 930may comprise a plastic material.

FIGS. 16A-16B depict cut-away side elevational and longitudinalcross-sectional views, respectively, of the ram and power assembly ofthe injection device of FIG. 10. As in the ram 502 described withrespect to the injection device 100, the ram 1102 may be directly orindirectly connected to the proximal housing 708, such that movement ofthe proximal housing 708 can be transmitted to the ram 1102. The ram1102 may be configured to transmit distal force on the proximal housing708 into different motions, depending on the stage of the injectionprocess. In a first stage, distal force on the proximal housing 708 maybe transmitted into distal motion of the syringe 704 and power assembly706 relative to the distal housing 710. In a second stage, distal forceon the proximal housing 708 may be transmitted into displacement of thecontents of the reservoir 914 of the syringe 704 (e.g., a formulationcomprising a therapeutic agent) through the lumen 908 of the needle 906.

In some variations, the ram 1102 may be configured such that theseeffects of distal force on the proximal housing 708 may occur in theorder described above. That is, the ram 1102 may be configured such thatdistal force on the proximal housing 708 may be transmitted first intodistal motion of the syringe 704 and power assembly 706 relative to thedistal housing 710, and then transmitted second into displacement of thecontents of the reservoir 914 of the syringe 704 (e.g., a formulationcomprising a therapeutic agent) through the lumen 908 of the needle 906.This may be desirable, for example, because it may allow the syringe 704to move distally such that the needle 906 may pierce a patient's tissuebefore the contents of the syringe cavity 904 are displaced through thelumen 908 of the needle 906.

In some variations, the ordering of effects of distal force on theproximal housing 708 may be due to different amounts of force that arerequired for each motion. For example, the ram 1102 may transmit distalforce on the proximal housing 708 into distal motion of the syringe 704and power assembly 706 relative to the distal housing 710 when the forceon the proximal housing 708 is above a first threshold (e.g., aboveabout 1N, above about 2N, above about 3N, above about 4N, above about5N, above about 6N, above about 7N, or higher); and the ram 1102 maytransmit distal force on the proximal housing 708 into displacement ofthe contents of the reservoir 914 of the syringe 704 through the lumen908 of needle 906 when the force on the proximal housing 708 is above ahigher second threshold (e.g., above about 1N, above about 2N, aboveabout 4N, above about 6N, above about 8N, above about 10N, above about12N, above about 14N, or higher). In some variations, the firstthreshold may be due to the proximal force from flanges on the baseretainer cap 1126 (described below) resisting distal movement of raminterlock 1226, to which the syringe 704 is attached, as described indetail below. The second threshold may be due to the force required toovercome a second set of flanges 1296 (described below) and to move therate control assembly 1204 of the power assembly 706 to an openconfiguration, as described in detail below. There may also be anintermediate threshold that may need to be overcome in order for theneedle 906 to be extended beyond the distal and 758 of the nose cone716. In some variations, this intermediate threshold may be due to twoflexures on the ram interlock 1226, which may interface with tworecesses in the distal housing 710. In should be appreciated that insome other variations, the ram 1102 may transmit distal force on theproximal housing 708 into different motion in different orders and bydifferent mechanisms. For example, in some variations the effect of thedistal force may be chosen by manual selection by the user. In shouldalso be appreciated that the ram may transmit distal force on theproximal housing into fewer or more different motions.

The ram 1102 may comprise a central portion comprising a plunger 1110and a ram crossbar 1112 at the proximal end 1114 of the plunger 1110.The plunger 1110 may be configured to be slidable within the syringecavity 904. The distal end 1116 of the plunger 1110 may be configured toengage with the seal 910 of the syringe 704. If the plunger 1110 ismoved distally relative to and within the syringe cavity 904, theplunger 1110 may push the seal 910 distally relative to and within thesyringe cavity 904. This movement of the seal 910 may decrease thevolume of the reservoir 914 containing the formulation comprising atherapeutic or diagnostic agent. Thus, distal motion of the plunger1110, and in turn of the seal 910, relative to and within the syringecavity 904 may cause the contents of the reservoir 914 to be displacedthrough the lumen 908 of the needle 906. The ram crossbar 1112 may beattached on its distal side to the proximal end 1114 of the plunger1110. The proximal surface 1118 of the ram crossbar 1112 may beconfigured to be able to sit adjacent to the inner surface 768 of theend cap 718 of the proximal housing 708, so that the ram crossbar 1112may serve as an indicator, as described above. The ram 1102 may comprisea bore hole 1120 extending through the ram crossbar 1112 and plunger1110, and may have a proximal opening 1122 at the proximal surface 1118of the ram crossbar 1112 and a closed distal end 1124 near the distalend 1116 of the plunger 1110. The bore hole 1120 may be configured tohouse at least a distal portion of a locking spring 1246 (described inmore detail below). The proximal end 1258 of the locking spring 1246 maybe attached or in contact with the inner surface 768 of the end cap 718of the proximal housing 708, while the distal end 1256 of the lockingspring 1246 may be attached to or in contact with the distal end 1124 ofthe bore hole 1120 of the plunger 1110. The locking spring 1246 may thusbe configured to transmit motion of the proximal housing 708 to the ram1102, in addition to acting as part of the rate control assembly 1204 ofthe power assembly 706, as described below. The plunger 1110 may furthercomprise two recesses 1140 at its distal end 1116. These recesses 1140may be configured to engage two flanges 1296 extending from a centrallumen 1228 of a ram interlock 1226 (described in more detail below). Theflanges 1296 may comprise inwardly facing proximal tabs 1298, which maybe configured to the engage the recesses 1140, which may cause theplunger 1110 to resist distal movement relative to the ram interlock1226.

The injection device 700 may further comprise a base retainer cap 1126.The distal side of the base retainer cap 1126 may be attached to theproximal side of the ram interlock 1226 (described below). As shown inFIGS. 16A-16B and in more detail in FIG. 16C, the base retainer cap 1126may comprise two flanges 1130, located on opposite sides of the mainbody 1132 of the base retainer cap 1126. The flanges 1130 may extendproximally and outwardly from the main body 1132, and may have proximaltabs 1134. The proximal tabs 1134 may engage recesses 780 on the innersurface of the proximal housing 708 in order to resist proximal motionof the proximal housing 708 relative to the distal housing 710 after theinjection device 700 has been assembled. The main body 1132 of the baseretainer cap 1126 may further comprise a central lumen 1136 and two sidelumens 1138. The central lumen 1136 may be configured to allow theplunger 1110 of the ram 1102 to move therethrough. The central lumen1136 may further comprise two recesses 1142 configured to allow theflanges 1296 of ram interlock 1126 to move therethrough (describedbelow). The two side lumens 1138 may be configured to allow a portion ofthe power assembly 706 to move therethrough, as described below. Thebase retainer cap 1126 may comprise any suitable material or materials,but in some variations, the base retainer cap 1126 may comprise aplastic material.

The injection device 700 may further comprise a ram interlock 1226. Theram interlock 1226, shown in more detail in FIG. 16D, may comprise acentral lumen 1228, configured to allow the plunger 1110 of the ram 1102to travel therethrough, and may comprise one side lumen 1236 on each oftwo opposite sides of the central lumen 1228, each configured to allowone of the two composite springs 1218 to travel therethrough, asdescribed in more detail below. The ram interlock 1126 may furthercomprise two flanges 1296 extending from the central lumen 1228, whichmay comprise inwardly facing proximal tabs 1298. In an initialconfiguration, the inwardly facing proximal tabs 1298 of the flanges1296 of the ram interlock 1126 may be engaged with recesses 1140 of theplunger 1110, as described above and shown in FIG. 16B, which may causethe plunger 1110 to resist distal movement relative to the ram interlock1226. The flanges 1296 may be resisted from flexing radially outward(such that the proximal tabs 1298 may disengage with recesses 1140 ofthe plunger 1110, which would allow the plunger 1110 to move distallyrelative to the ram interlock 1226) because in the initial configurationthe distal face of the base retainer cap 1126 is seated against theproximal face of the ram interlock 1226, such that the flanges 1296 ofthe ram interlock 1226 are located within recesses 1142 of the baseretainer cap 1126. The base retainer cap 1126 may thus exert radiallyinward pressure on the flanges 1296 to resist them moving radiallyoutward. This may create hoop stress in the central lumen 1228 of theram interlock 1226.

Application of distal force on the proximal housing 708 may cause theproximal housing 708 to be moved distally. If the distal housing 710 isheld in place (e.g. by pressing the distal end 758 of the nose 716 ofthe distal housing 710 against a patient's tissue), the proximal housing708 may be moved distally relative to the distal housing 710. Themovement of the proximal housing 708 may be transferred via the lockingspring 1246 to cause the power assembly 706 and syringe 704 to slidedistally relative to the distal housing 710 if the distal force on theproximal housing 708 is above the necessary force threshold. Morespecifically, distal force on the proximal housing 708 may cause distalmotion of the locking spring 1246, and in turn, distal motion of thepower assembly 706. Distal motion of the power assembly 706 may in turncause distal motion of the syringe 704. This may move the syringe 704from a retracted position (shown in FIGS. 12A-12B) into an extendedposition (shown in FIG. 12D-12F), as described above with respect tosyringe 104 of injection device 100. As the distal tip 924 of the needle906 approaches the distal opening 712 of the nose 716, the needle shroud802 of the needle safety assembly 800 may be unlocked from a retractedposition, as described in detail above and shown in FIGS. 13A-13D. Asthe distal tip 924 of the needle 906 moves to extend beyond the distalend 758 of the nose 716, the needle 906 may pierce tissue pressedagainst the distal end 758 of the nose 716. The syringe 704 may continueto move distally relative to the distal housing 710 until the syringe704 has reached an extended position, at which point distal motion ofthe syringe 704 may be stopped by engagement of the syringe sleeve 930with a portion of the nose 716. At an extended position, the distal tip924 of the needle 906 may have reached the desired depth, as describedabove. In some variations, the injection device 700 may comprise aninsertion detent, which may cause the movement of the distal tip 924 ofthe needle 906 to occur at a specific rate during insertion, in order toachieve a desired insertion speed into tissue, as described above.

It should be noted that the power assembly 706 and syringe 704 may movedistally together with distal force on the proximal housing 708 in aparticular stage of the injection process, rather than the powerassembly 706 acting on the syringe 704 (e.g., by moving the plunger 1110distally within the syringe cavity 904 to act on the seal 910 anddisplace the contents of the reservoir 914), due to the relative amountsof force required to move the power assembly 706 and the syringe 704relative to the distal housing 710, and to move the ram 1102 relative tothe syringe 704. That is, the amount of force required to move thesyringe 704 to an extended position may be less than the amount of forcerequired to cause distal motion of the ram 1102 relative to the syringe704. In some variations, the ram interlock 1226 and base retainer cap1126 may prevent distal motion of the ram 1102 relative to the syringe704 until the syringe 704 is in an extended position. The flanges 1296of the ram interlock 1226 may be located within recesses 1142 of thebase retainer cap 1126, which may exert radially inward pressure on theflanges 1296 to resist them flexing radially outward to disengage withrecesses 1140 of the plunger 1110, as described above. As the syringe704 moves toward an extended configuration, however, the proximalhousing 708, power assembly 706, and ram interlock 1226 may movedistally with the syringe 704 relative to the distal housing 710, whilethe base retainer cap 1126 may remain fixed relative to the distalhousing 710. The flanges 1296 may be configured to have a length suchthat they may remain constrained by the base retainer cap 1126 until thesyringe 704 has reached an extended position.

After the power assembly 706 and syringe 704 have moved distallyrelative to the distal housing 710 such that the syringe 704 is in anextended position and the distal tip 924 of the needle 906 is at thedesired depth, and, correspondingly, the flanges 1296 of the raminterlock 1226 may be no longer constrained by the base retainer cap1126, additional distal force on the proximal housing 708 may betransmitted into distal motion of the ram 1102 relative to the syringecavity 904 if the force is above the necessary force threshold. When theforce is above the necessary force threshold, the plunger 1110 and seal910 may be moved distally within the syringe cavity 904, which maydecrease the volume of the reservoir 914 and displace the contents ofthe reservoir 914 through the lumen 908 of the needle 906, as describedabove with respect to syringe 104 of injection device 100. Distal forceon the proximal housing 708 may continue to cause the contents of thereservoir 914 to be displaced through the lumen 908 of the needle 906until the seal 910 has traveled to the distal end 918 of the syringecavity 904 (shown in FIGS. 12D-12E). In some variations, the thresholdforce required to move the plunger 1110 and seal 910 distally within thesyringe cavity 904 may be due to the flanges 1296 of the ram interlock1226. As described above, the ram interlock 1126 may comprise twoflanges 1296 extending from the central lumen 1228, which may compriseinwardly facing proximal tabs 1298. In an initial configuration, theinwardly facing proximal tabs 1298 of the flanges 1296 of the raminterlock 1126 may be engaged with recesses 1140 of the plunger 1110,which may cause the plunger 1110 to resist distal movement relative tothe ram interlock 1226. When a threshold force is applied, however, theflanges 1296 may flex radially outward such that the proximal tabs 1298may disengage with recesses 1140 of the plunger 1110, and thus may allowthe plunger 1110 to move distally relative to the ram interlock 1226,subject to the rate control assembly of the power assembly 706,described below. If the distal force on the proximal housing 108 isreleased while the power assembly 706 and syringe 704 are moving from aretracted position to an extended position, the power assembly 706 andsyringe 704 may stay in place relative to the distal housing 710.

As described above with respect to the power assembly 106 of injectiondevice 100, the power assembly may provide an injection force sufficient(alone or in addition to injection force supplied by the user) to injecta given volume of a given formulation through a given size needle in agiven time, as described in detail with regard to power assembly 106.Like the power assembly 106, power assembly 706 may comprise a storedenergy source and a rate control assembly. As in the power assembly 106described with respect to injection device 100, the power assembly 706may comprise a stored energy source 1202, which may be configured toprovide force to displace the contents of reservoir 914 of the syringe704 through the lumen 908 of the needle 906, and a rate control assembly1204, which may comprise a braking assembly that may limit or restrictthe stored energy source 1202 from contributing to the displacement ofthe contents of the reservoir 914 of the syringe 704 through the lumen908 of the needle 906. Returning to FIGS. 16A-16B, the stored energysource 1202 may comprise one or more springs to provide injection force.In the injection device 700, the springs of the stored energy source1202 may pull the ram 1102 distally in order to cause the contents ofthe reservoir 914 of the syringe 704 to be displaced through the lumen908 of the needle 906. In some variations, the springs may be compositesprings in order to decrease the total length of the spring required toproduce a desired force. Such a composite spring may comprise anextension spring located coaxially within a compression spring. Itshould be appreciated, however, that in other embodiments, the springsmay not comprise composite springs, and may instead comprise, forexample, a single extension spring or a single compression spring;further, in other embodiments, an injection device may comprise only onecomposite spring, or may comprise more than two composite springs, suchas two, three, four, or more composite springs.

The two composite springs 1218 of the stored energy source 1202 may eachhave a compression spring 1220 located coaxially about an extensionspring 1206. It should be appreciated that in other variations, theextension spring 1206 may be located coaxially within the compressionspring 1220. In each of the two composite springs 1218, the proximal end1222 of the compression spring 1220 may be located distally to theproximal end 1214 of the extension spring 1206, and the proximal end1222 of the compression spring 1220 may be attached to the ram interlock1226. The proximal end 1214 of the extension spring 1206 may be attachedto the ram crossbar 1112. The distal end 1224 of the compression spring1220 and the distal end 1216 of the extension spring 1206 may beconnected to each other directly or indirectly at a composite springinterface 1230. In some variations, the composite spring interface 1230may comprise an intermediate component, such as but not limited to aplastic bushing, that may engage the distal end 1224 of the compressionspring 1220 and the distal end 1216 of the extension spring 1206. Inother variations, the distal end 1216 of the extension spring 1206 maycomprise a wireformed loop having a larger diameter than the compressionspring 1220, and the compression spring 1220 may be inserted into thedistal end 1216 of the extension spring 1206 to engage the compressionspring 1220 and the extension spring 1206. In yet other variations, theextension spring 1206 and compression spring 1220 may be formed as anintegrated wireform using a continuous wire.

The spring rates of the extension spring 1206 and compression springs1220 may be chosen to deliver an appropriate force based on theformulation viscosity, needle choice, volume, and desired injectiontime, as described above. In some variations, for example, the springmay be configured to deliver a force of up to about 5N, about 10N, about15N, about 20N, about 25N, about 30N, about 35N, about 40N, about 45N,about 50N, about 55N, about 60N, about 65N, about 70N, about 75N, about80N, about 85, or about 90N when the composite spring 1218 is initiallyreleased. In some variations, the composite springs 1218 and/or theextension springs 1220 may comprise music wire, but it should beappreciated that the springs may be made of any suitable material ormaterials.

In some variations, the composite springs 1218 may additionally comprisea composite spring sleeve 1232, but need not. In variations havingcomposite spring sleeves, the composite spring sleeves 1232 may comprisea cylindrical wall 1234 that may separate the extension spring 1206 andthe compression spring 1220. In some variations, the composite springsleeves 1232 may assist in providing spring guidance. The compositespring sleeves 1232 may pass through the side lumens 1236 on each sideof the central lumen 1228 of the ram interlock 1226, and they may passthrough the two side lumens 1138 of the base retainer cap 1126. Thedistal end 1240 of the composite spring sleeve 1232 may serve as thecomposite spring interface 1230, and as such, may have both the distalend 1224 of the compression spring 1220 and the distal end 1216 of theextension spring 1206 attached to it. In some variations, the raminterlock 1226 and/or spring sleeves 1232 may comprise a plasticmaterial, but it should be appreciated that the ram interlock 1226and/or spring sleeves 1232 may be made of any suitable material ormaterials.

The extension springs 1206 may bias the composite spring interfaces 1230and the ram crossbar 1112 toward each other, while the compressionspring 1220 may bias the ram interlock 1226 and the composite springinterfaces 1230 away from each other. The joint effect of the extensionsprings 1206 and compression springs 1220 of the composite springs 1218may therefore be to bias the ram interlock 1226 and the ram crossbar1112 toward each other. By biasing the ram interlock 1226 and the ramcrossbar 1112 toward each other, the composite springs 1218 may thusbias the plunger 1110 distally through the central lumen 1228 of the raminterlock 1226. The plunger 1110 may be configured to fit slidablywithin the syringe cavity 904 and to press against the seal 910, whichmay in turn cause the contents of the reservoir 914 of the syringe 704to be displaced through the lumen 908 of the needle 906, as described indetail above with respect to syringe 104 of injection device 100.

The distal movement of the plunger 1110 to press against the seal 910 ofthe syringe 704, however, may at times be resisted or limited by therate control assembly 1204. As described above with respect to injectiondevice 100, the rate control assembly may be moveable between a closedconfiguration and an open configuration. When the rate control assemblyis in a closed configuration, the rate control assembly may limit orrestrict the displacement of the contents of the reservoir of thesyringe. When the rate control assembly is in an open configuration, therate control assembly may not limit or restrict the displacement of thecontents of the reservoir of the syringe. In some variations, the ratecontrol assembly may be configured to limit or restrict the displacementof the contents of the reservoir of the syringe by limiting orrestricting the distal motion of a plunger within the syringe cavitywhen in a closed configuration. When in an open configuration, the ratecontrol assembly may not limit or restrict the distal motion of aplunger within the syringe cavity, thus allowing the stored energysource to act upon the plunger to move it distally relative to andwithin the syringe cavity, which may move the seal of the syringedistally within the syringe cavity to displace the contents of thereservoir through the lumen of the needle.

As shown in FIG. 16A, the rate control assembly 1204 may comprise a cordtensioning system 1242. The cord tensioning system 1242 may resist theeffects of the stored energy source 1202 described above. The cordtensioning system 1242 may be reversibly and selectively moved betweentensioned (the “closed” configuration of the rate control assembly) andreleased (the “open” configuration of the rate control assembly)configurations. Generally, the cord tensioning system 1242 may comprisea tensioning cord 1244 in addition to the locking spring 1246 and raminterlock 1226 mentioned above. When the cord tensioning system 1242 isin a tensioned configuration, the locking spring 1246 may generate atensioning force on the tensioning cord 1244 of sufficient magnitude tobe capable of resisting distal movement of the ram 1102 due to thestored energy source 1202. Sufficient tensioning force in the tensioningcord 1244 may be achieved by wrapping the tensioning cord 1244 around abollard 1288. In some variations, the bollard 1288 may comprise aportion of the ram interlock 1226, as will be described in more detailbelow. When the cord tensioning system 1242 is in a releasedconfiguration, the cord tensioning system 1242 may allow the distalforce on the ram 1102 from the composite springs 1218 to urge theplunger 1110 of the ram 1102 distally, as will be described in moredetail below. In some variations, the cord tensioning system 1242 mayoptionally further comprise a float 1248, a locking spring retainer1250, and a locking spring cap 1252, which will be explained in moredetail below.

As shown in FIGS. 16A-16B, the locking spring 1246 may comprise acompression spring 1254. As described above, at least a distal portionof the locking spring 1246 may be located within the bore hole 1120 ofthe plunger 1110. The distal end 1256 of the locking spring 1246 may beattached to or in contact with the distal end 1124 of the bore hole 1120of the plunger 1110. Alternatively, in some variations, at least adistal portion of the locking spring 1246 may be housed in a lockingspring retainer 1250. The distal end of the locking spring retainer 1250may be located proximally to the distal end 1124 of the bore hole 1120,or in other variations, it may be attached to or in contact with thedistal end 1124 of the bore hole 1120. In some variations, the lockingspring retainer 1250 may comprise a deep drawn metal. In somevariations, the locking spring retainer 1250 may comprise a hole in itsdistal end, which may allow flow of a viscous damping fluid located inthe bore hole 1120, and as such, may dampen the motion of the lockingspring retainer 1250 under the force of the locking spring 1246. Theproximal end 1258 of the locking spring 1246 may be attached or incontact with the inner surface 768 of the end cap 718 the proximalhousing 708. The locking spring 1246 may thus bias the plunger 1110 awayfrom the end cap 718 of the proximal housing 708. In some variations,the locking spring 1246 may have a spring rate of about 0.1N/mm to0.2N/mm, 0.2N/mm to 0.3N/mm, 0.3N/mm to 0.4N/mm, 0.4N/mm to 0.5N/mm,0.5N/mm to 0.6N/mm, 0.6N/mm to 0.7N/mm, 0.7N/mm to 0.8N/mm, 0.9N/mm to1N/mm, or greater. In some variations, the proximal end 1258 of thelocking spring 1246 may be housed in a locking spring cap 1252. Thelocking spring cap 1252 may serve to hide the proximal end 1258 of thelocking spring 1246 from view through the end cap 718, for example invariations in which all or a portion of the end cap 718 is made of aclear or translucent material.

As shown in FIG. 17, the rate control assembly 1204 may further comprisea tensioning cord 1244. The ends of the tensioning cord 1244 may beattached to a float 1248 that may be fixedly attached to the proximalhousing 708 (not shown), while the middle of the tensioning cord 1244may be wound around the ram interlock 1226 at two points and attached inbetween those two points to the distal end 1116 of the plunger 1110. Itshould be appreciated that in some variations, the tensioning cord 1244may be directly attached to the proximal housing 708, instead of to afloat. The locking spring 1246, by biasing the plunger 1110 away fromthe end cap 718 of the proximal housing 708 (not shown), may generatetension in the tensioning cord 1244, thus resisting distal movement ofthe plunger 1110. More specifically, the float 1248 may be attached tothe proximal housing 708 via latches that may snap into matchingrecesses in the proximal housing 708. In some variations, the float 1248may comprise a plastic material, though it should be appreciated thatthe float 1248 may comprise any suitable material or materials.

The first end 1254 of the tensioning cord 1244 may be attached to thefloat 1248 on a first side of the plunger 1110. The first end 1254 ofthe tensioning cord 1244 may be attached in any suitable manner to thefloat 1248. For example, in some variations, the first end 1254 of thetensioning cord 1244 may be attached to the float 1248 by beingencapsulated into the plastic material, for example by beinginsert-molded into the float 1248. In other variations, the first end1254 of the tensioning cord 1244 may be fitted with a lug or ferrule,which may in turn be attached to a receiving socket in the float 1248. Afirst portion 1272 of the tensioning cord 1244 may extend distally fromthe float 1248 toward the ram interlock 1226. The ram interlock 1226 maycomprise one or more bollards 1288 that may allow the tensioning cord1244 to be wrapped around the ram interlock 1226 in a manner generatingfriction between the tensioning cord 1244 and ram interlock 1226. Insome variations, the ram interlock 1226 may comprise a first protrusion1264 and a second protrusion 1266 located on opposite sides of the raminterlock 1226. The tensioning cord 1244 may have a second portion 1274that may wrap around a rounded side 1290 of the first protrusion 1264.The tensioning cord 1244 may have a third portion 1276 that may travelfrom the first protrusions 1264 to the distal end 1116 of the plunger1110. The distal end 1116 of the plunger 1110 may comprise one or morefeatures that may allow the tensioning cord 1244 to be attached to itsdistal end 1116. In some variations, the distal end of the plunger 1110may comprise a slot 1756 across the distal face 1754 of the plunger1110, through which a fourth portion 1278 of the tensioning cord 1244may be placed. A fifth portion 1280 of the tensioning cord 1244 may exitthe slot 1756 of the plunger 1110 and extend toward the secondprotrusion 1266 (not shown). A six portion 1282 of the tensioning cord1244 may wrap around a rounded side 1292 of the second protrusion 1266(not shown). While in the variation shown the first protrusion 1264 andsecond protrusion 1266 may comprise first and second horizontalcylindrical segments 1268 and 1270 (not shown), where the first andsecond horizontal cylindrical segments 1268 and 1270 may be orientedwith their rounded sides facing distally, it should be appreciated thatfirst and second protrusions 1264 and 1266 of the ram interlock 1226 maybe shaped such that the protrusions are rounded at the points of contactwith the tensioning cord 1244, and therefore in some variations maycomprise full cylindrical segments. Finally, the tensioning cord 1244may have a seventh portion 1284 that may extend proximally from the raminterlock 1226 toward the float 1248, where the second end 1256 of thetensioning cord 1244 may be attached to the float 1248 on the secondside of the plunger 1110 (not shown). The second end 1256 may beattached to the float 1248 in any suitable manner, including in themanners described above with respect to first end 1254. In othervariations, the first end 1254 and second end 1256 may be connected(e.g., the tensioning cord 1244 may be a closed loop, or the first andsecond ends 1254 and 1256 may be spliced, knotted, or welded together),and the tensioning cord 1244 may extend around the float 1248 to secureit. In some of these variations, the tensioning cord 1244 may sit in areceiving groove in the float 1248.

By wrapping the tensioning cord 1244 as described through the slot 1756on the distal face 1754 of the plunger 1110, the tension in thetensioning cord 1244 may resist distal movement of the plunger 1110through the central lumen 1228 of the ram interlock 1226 due to thebiasing force from the stored energy source 1202. Due to frictionbetween the tensioning cord 1244 and the first and second protrusions1264 and 1266 of the ram interlock 1226, the cord tensioning system 1242may be able to resist higher forces from the stored energy source 1202than may be provided by the locking spring 1246. Under the principle ofthe capstan equation (also known as Eytelwein's formula), tension on acord (e.g., the tensioning cord 1244) may be different on either side ofa static cylinder (e.g., first and second protrusions 1264 and 1266 ofthe ram interlock 1226), such that a holding force on one side of thestatic cylinder (e.g., the tension supplied by the locking spring 1246)may carry a larger loading force (e.g., the force supplied by thecomposite springs 1218). The relationship between the holding force andthe loading force is dictated by the coefficient of friction between thecord and the static cylinder, as well as the wrap angle—the angle aroundwhich the cord contacts the static cylinder. In the cord tensioningsystem 1242, the tensioning cord 1244 and ram interlock 1226 maycomprise any materials having suitable coefficients of friction, such asbut not limited to a tensioning cord 1244 comprising aramid fibers andfirst and second protrusions 1264 and 1266 comprising polycarbonate. Insome variations, the coefficient of friction between these two materialsmay be about 0.1 to 0.2, about 0.2 to 0.3, about 0.3 to 0.4, about 0.4to 0.5, or greater. Additionally, it may be desirable for the tensioningcord 1244 to comprise a material having suitable ability to holdsustained loads, as well as resist creep and stretch, such as but notlimited aramid fibers. The tensioning cord 1244 may be wrapped aroundthe first and second protrusions 1264 and 1266 of the ram interlock 1226for wrap angles sufficient to generate the desired relationship betweenthe holding force and the loading force. In some variations, the wrapangle may be approximately 180 degrees. In other variations, the wrapangle may be over 360 degrees, for example 720 degrees; that is, thetensioning cord 1244 may be wrapped multiple times around the first andsecond protrusions 1264 and 1266 of the ram interlock 1226.

The cord tensioning system 1242 may be biased toward the tensionedconfiguration, such that when no distal force is applied to the proximalhousing 708, the cord tensioning system 1242 may resist or limit thestored energy source 1202 from contributing to the displacement of thecontents of the reservoir 914 of the syringe 704 through the lumen 908of the needle 906 by applying a proximal force to the distal end 1116 ofthe plunger 1110 of the ram 1102, as described above.

Although the cord tensioning system 1242 may be biased toward atensioned configuration as described above, the cord tensioning system1242 may be moved toward the released configuration by reducing orreleasing the tension on first portion 1272 and seventh portion 1284 ofthe tensioning cord 1244 (described above). The tension on the firstportion 1272 and seventh portion 1280 of the tensioning cord 1244 may bereduced or released by reducing the distance between the first andsecond ends 1254 and 1256 of the tensioning cord 1244 and the first andsecond protrusions 1264 and 1266 of the ram interlock 1226. Thisdistance may be reduced by applying distal force to the proximal housing708. When a distal force is applied to the proximal housing 708 whilethe distal housing 710 is held in place (e.g. by pressing the distal end758 of the nose 716 of the distal housing 710 against a patient'stissue), the proximal housing 708 and the float 1248 may be moveddistally relative to the first and second protrusions 1264 and 1266 ofthe ram interlock 1226. When the tension on the first portion 1272 andseventh portion 1284 of the tensioning cord 1244 is reduced, the tensionthat can be held by the third portion 1276 and the fifth portion 1280 ofthe tensioning cord 1244 may be correspondingly reduced, based on thecapstan equation described above. As a result, the distal force on theplunger 1110 of the ram 1102 due to the stored energy source 1202 may nolonger be able to be partially or fully opposed by the tensioning cord1244 running through the slot 1756 on the distal face 1754 of theplunger 1110, and the tensioning cord 1244 may slip around the first andsecond protrusions 1264 and 1266 of the ram interlock 1226, which mayallow the plunger 1110 to move distally into the syringe cavity 904, asdescribed above and shown in FIG. 12E. This may in turn urge the seal910 distally to displace the contents of the reservoir 914 through thelumen 908 of the needle 906, as described above.

In some variations, the tensioning cord 1244 may begin to slip aroundthe first and second protrusions 1264 and 1266 of the ram interlock1226, which may allow the plunger 1110 to move distally into the syringecavity 904, before the tension on the first portion 1272 and seventhportion 1284 of the tensioning cord 1244 is reduced to zero. In such acase, a portion of the force from the composite springs 1218 may urgethe plunger 1110 to move distally within the syringe cavity 904. If auser applies distal force to the proximal housing 708 sufficient toreduce the tension on the first portion 1272 and seventh portion 1284 ofthe tensioning cord 1244 to zero (e.g., by counterbalancing the fullforce from the locking spring 1246), the full force from the compositesprings 1218 may urge the plunger 1110 to move distally within thesyringe cavity 904. If a user applies distal force to the proximalhousing 708 beyond the amount needed to reduce the tension on the firstportion 1272 and seventh portion 1284 of the tensioning cord 1244 tozero, the additional distal force on the proximal housing 708 may betransferred into additional force urging the plunger 1110 to movedistally within the syringe cavity 904.

If the distal force on the proximal housing 708 is released, the bias ofthe proximal housing 708 away from the ram interlock 1226 due to thelocking spring 1246 (described above) may cause the proximal housing 708to move distally away from the ram interlock 1226. The float 1248 may inturn move distally away from the ram interlock 1226, which may restoretension in the first portion 1272 and seventh portion 1284 of thetensioning cord 1244 and return the cord tensioning system 1242 to atensioned configuration. The rate control assembly 1204 may then resistmotion due to the stored energy source 1202. This may allow the user toselectively and reversibly start and stop, or increase or decrease thespeed of, the injection process. FIG. 22 shows an illustrative graph ofthe user force required to perform an injection using an injectiondevice having a power assembly similar to the power assembly 706 of theinjection device 700, illustrating the initial actuation force andincreasing actuation force throughout the stroke during the injectionprocess. The graph represents the applied force required to maintainsubstantially constant distal motion of the housing 708 (and thus of theplunger 1110) in order to maintain a substantially constant rate ofinjection. As shown, the composite spring may relax during the injectionstroke, therefore exerting a decreasing force; thus, to maintain asubstantially constant rate of injection, the applied force may need toincrease with progress of the injection (and thus increase as a functionof time, as shown). However, it should be noted that the user need notmaintain a substantially constant rate of injection. As shown, anapplied force of approximately 4N is required in the given configurationto sufficiently relax the tensioning cords in order to allow theinjection to begin, and subsequently a lesser force may be required tocontinue the injection, although the resulting injection rate may beslower. It should be noted that this graph is merely illustrative of theuser force required for a similar device, and is not meant to indicatethat the injection device 700 may or must conform to thisrepresentation.

In some variations, the injection device 700 may comprise anautocomplete mechanism, as described with respect to injection device100. In some variations, the autocomplete mechanism may be based on arelaxation of the locking spring 1246. As described above, the lockingspring 1246 may generate a tensioning force on the tensioning cord 1244.When the tension is released, the seal 910 may be able to move distallyto displace the contents of the reservoir 914 through the lumen 908 ofthe needle 906. Thus, the injection may autocomplete by reducing thetensioning force on the tensioning cord 1244 due to the locking spring1246. In some variations, the tensioning force on the tensioning cord1244 due to the locking spring 1246 may be reduced by increasing thedistance between the proximal and distal ends of the locking spring1246. In some of these variations, this can be achieved by locating thelocking spring retainer 1250 within the bore hole 1120 of the ram 1102such that the distal end of the locking spring retainer 1250 is locatedproximally to the distal end 1124 of the bore hole 1120 beforeautocompletion. Because the distal portion of the locking spring 1246may be housed in the locking spring retainer 1250, the distal end of thelocking spring 1246 may thus be located proximally to the distal end1124 of the bore hole 1120. When autocompletion is initiated, thelocking spring retainer 1250 may move distally within the bore hole1120, which may in turn allow the distal end of the locking spring 1246to move distally within the bore hole 1120, relaxing the locking spring1246. In some variations, autocompletion may be initiated by the raminterlock 1226. The locking spring retainer 1250 may be held at aposition proximally to the distal end 1124 of the bore hole 1120 by twohooks (not shown) on the locking spring retainer 1250 that extendoutwardly and into corresponding openings (not shown) in the ram 1102.When the injection has proceeded such that the ram 1102 has moveddistally such that the openings in the bore hole 1120 are aligned withthe inwardly facing proximal tabs 1298 of the flanges 1296 of the raminterlock 1226, the tabs 1298 may enter the openings in the ram 1102 andmay apply an inward force that pushes the hooks on the locking springretainer 1250 such that they disconnect from the openings in the ram1102. When the hooks disconnect from the openings, the locking springretainer 1250 may move distally within the bore hole 1120 to the distalend 1124 of the bore hole, due to the biasing force from the lockingspring 1246. As described above, when the locking spring retainer 1250moves distally, the distal end of the locking spring 1246 may also movedistally, which may in turn relax the locking spring 1246 and may causethe injection to autocomplete.

In some variations, one or more of the elements of injection device 700may optionally comprise clocking features to correcting orient theelements relative to each other, as described above with respect toinjection device 100. Additionally or alternatively, in variations inwhich the housing 702 has an elliptical cross-section, the ellipticalcross-section may contribute to the correct orientation of the housingelements.

In some variations, it may be desirable to assemble portions of theinjection device 700 in a particular order. For example, in somevariations, a first portion of the injection device 700 may be assemblyby attaching the tensioning cord 1244 may be attached at its first end1254 and second end 1256 to the float 1248. The tensioning cord 1244 maythen be wrapped around the bollards 1288 of the ram interlock 1226—morespecifically, the second portion 1274 and sixth portion 1282 may bewrapped around the first protrusion 1264 and the second protrusion 1266of the ram interlock 1226, respectively. The base retainer cap 1126 maythen be placed in line with the ram interlock 1226. Then, the ram 1102may be put into place such that the fourth portion 1278 of the cord isengaged with the slot 1756 on the distal face 1754 of the plunger 1110,and the ram may be secured by lowering the base retainer cap 1126 ontothe ram interlock 1226. The composite springs 1218 may then beinstalled, which may be done by inserting each composite spring 1218proximally through the side lumens 1236 of the ram interlock 1226 andside lumens 1138 of the base retainer cap 1126 and attaching theproximal end of the composite spring 1218 to the ram crossbar 1112. Asecond portion of the injection device 700 may then be assembled byattaching the nose 716 to the remainder of the distal housing 710, suchas by sonic welding. The compression spring 820 of the needle safetyassembly 800 may then be snapped into the nose 716 of the housing 710,and the locking assembly 826 may be snapped into the nose 716 via thelocking assembly 826. A third portion of the injection device 700 may beassembled by placing the syringe sleeve 930 around a pre-filled syringe704. The third portion may then be attached to the first portion of theinjection device 700 by attaching the syringe sleeve 930 to the raminterlock 1226 via the latches 946 on the proximal lip 954 of thesyringe sleeve 930. The attached first and third portions may then beinserted into the second portion of the injection device 700 (comprisingthe distal housing 710). The locking spring retainer 1250, lockingspring 1246, and locking spring cap 1252 may then be inserted into thebore hole 1120 of the ram 1102. The proximal housing 702 may then beattached, which may be done by snapping together the float 1248 and theproximal housing 708 via the latches 1260 on the float 1248. The rigidneedle shield 922 and cap 772, in variations having a cap 772, may alsobe installed. It should be appreciated that this order of assembly isonly illustrative, and that the elements of the injection device 700 maybe assembled in other orders. It should also be appreciated that theassembly process may include additional elements not included in thedescription above, and that not all of the elements described as beingassembled need be incorporated into the device.

Another embodiment of an injection device 1300 is depicted in FIGS. 18and 19A-19D, comprising a housing 1302, a syringe 1304, and a powerassembly 1306. The housing 1302 may be similar to the housing 102,described above with respect to injection device 100, and may have thesame components, configurations, and functions. In some variations, thismay optionally comprise a cap 1348, which may be similar to the cap 148described above with respect to injection device 100, and may have thesame components and functions as described above.

FIGS. 19A-19G illustrate longitudinal cross-sectional views of theembodiment of an injection device of FIG. 17 in various stages duringuse. FIG. 19A illustrates the device before use. FIG. 19B illustratesthe device with the rigid needle shield and cap removed. FIG. 19Cillustrates the device with the syringe in a partially extendedposition. FIG. 19D illustrates the device with the syringe in a fullyextended position. FIG. 19E illustrates the device with the plungermoved partially toward the distal position within the syringe cavity.FIG. 19F illustrates the device with the plunger in the distal positionwithin the syringe cavity. FIG. 19G illustrates the device with theneedle shroud extended. Like the injection device 100, the injectiondevice 1300 may comprise a needle safety assembly 1400 that may bemovable between a retracted position (shown in FIGS. 19A-19B) and anextended position (shown in FIGS. 19D-19G), as described in detail abovewith regard to needle safety assembly 200. The needle safety assembly1400 may have the same components, positions, and functions as theneedle safety 200 described with respect to injection device 100.

The housing 1302 may also comprise an indicator that, like theindicators described with respect to the injection device 100, mayindicate the progress or completion of the injection, as described indetail above, and may have activated and inactivated configurations. Insome variations of the injection device 1300, the end-of-dose indicatormay comprise a flag. The flag may be spring-biased and may be releasedby relative motion between the flag and the housing 1302. When theindicator is in an activated configuration, it may be visible throughthe end cap 1318 of the proximal housing 1308.

The syringe 1304 of the injection device 1300 may be similar to thesyringes 104 and 704 described above with respect to injection devices100 and 700, and may have the same components, positions, and functionsas described above.

The injection device 1300 may further comprise a syringe sleeve 1630.The syringe sleeve 1630 may be attached to the distal housing 1310 via aset of flexures and protrusions (not shown) that may hold the syringesleeve 1630 relative to the ledge 1356 extending radially inward fromthe distal end 1314 of the distal housing 1310. The syringe 1304 may beslidably disposed with the syringe sleeve 1630. The syringe sleeve 1630may comprise a distal portion 1632 and a proximal portion 1634. Thedistal portion 1632 may be configured to fit slidably around the syringebody 1602. The proximal portion 1634 may have a larger diameter (ormaximum distance transverse to the longitudinal axis) than the distalportion 1632. In some variations, the syringe sleeve may comprise atransparent or translucent material, such as a plastic. The proximalportion 1634 of the syringe sleeve 1630 may be configured to engage witha syringe cap 1836 (described below). The proximal portion 1634 of thesyringe sleeve 1630 may comprise recess, slot, or other indentationconfigured to mate with tabs on the distal end of latches on the syringecap 1836, as described below.

As in the embodiments of the injection device 100 and 700, the ram 1702of the injection device 1300 may be configured to transmit distal forceon the proximal housing 1308 into different motions, depending on thestage of the injection process. In a first stage, distal force on theproximal housing 1308 may be transmitted into distal motion of thesyringe 1304 and power assembly 1306 relative to the distal housing1310. In a second stage, distal force on the proximal housing 1308 maybe transmitted into displacement of the contents of the reservoir 1614of the syringe 1304 (e.g., a formulation comprising a therapeutic agent)through the lumen 1608 of the needle 1606.

In some variations, the ram 1702 may be configured such that theseeffects of distal force on the proximal housing 1308 may occur in theorder described above. That is, the ram 1702 may be configured such thatdistal force on the proximal housing 1308 may be transmitted first intodistal motion of the syringe 1304 and power assembly 1306 relative tothe distal housing 1310, and then transmitted second into displacementof the contents of the reservoir 1614 of the syringe 1304 (e.g., aformulation comprising a therapeutic agent) through the lumen 1608 ofthe needle 1606. This may be desirable, for example, because it mayallow the syringe 1304 to move distally such that the needle 1606 maypierce a patient's tissue before the contents of the syringe cavity 1604of the syringe 1304 are displaced through the lumen 1608 of the needle1606.

In some variations, the ordering of effects of distal force on theproximal housing 1308 may be due to different amounts of force that arerequired for each motion. For example, the ram 1702 may transmit distalforce on the proximal housing 1308 into distal motion of the syringe1304 and power assembly 1306 relative to the distal housing 1310 whenthe force on the proximal housing 1308 is above a first threshold (e.g.,above about 1N, above about 2N, above about 3N, above about 4N, aboveabout 5N, above about 6N, above about 7N, or higher); and the ram 1702may transmit distal force on the proximal housing 1308 into displacementof the contents of the reservoir 1614 of the syringe 1304 through theneedle 1606 when the force on the proximal housing 1308 is above ahigher second threshold (e.g., above about 5N, above about 10N, aboveabout 15N, above about 20N, above about 25N, or higher). In somevariations, the thresholds may be due to the proximal forces fromfriction on the syringe 1304 and ram 1702, respectively. It should beappreciated that in some other variations, the ram 1702 may transmitdistal force on the proximal housing 1308 into different motions indifferent orders and by different mechanisms. For example, in somevariations the effect of the distal force may be chosen by a mechanismfor manual selection by the user. In should also be appreciated that theram 1702 may have fewer or more motions into which it may transmitdistal force onto the proximal housing 1308.

The ram 1702 may comprise a plunger 1710. The plunger 1710 may beconfigured to be slidable through the lumen 1842 of the syringe cap 1836(described below), and may be configured to be slidable within thesyringe cavity 1604 of the syringe 1304. The distal end 1716 of theplunger 1710 may be configured to engage with the seal 1610 of thesyringe 1304. If the plunger 1710 is moved distally relative to andwithin the syringe cavity 1604, the plunger 1710 may push the seal 1610distally relative to and within the syringe cavity 1604. This movementof the seal 1610 may decrease the volume of the reservoir 1614containing the formulation comprising a therapeutic or diagnostic agent.Thus, distal motion of the plunger 1710, and in turn the seal 1610,relative to and within the syringe cavity 1604 may cause the contents ofthe reservoir 1614 to be displaced through the lumen 1608 of the needle1606. The plunger 1710 may comprise an inner tube 1742 located coaxiallywithin an outer tube 1744. The inner tube 1742 and outer tube 1744 mayform an inner lumen 1746 within the inner tube 1742, and an outerannular lumen 1748 between the inner tube 1742 and outer tube 1744. Insome variations, the outer annular lumen may be divided into two or more(e.g., three, four, etc.) radial segments. The inner lumen 1746 andouter annular lumen 1748 may cooperate with the power assembly 1306 todirect pressure flow from the stored energy source 1802, as described indetail below.

Application of distal force on the proximal housing 1308 may cause theproximal housing 1308 to be moved distally. If the distal housing 1310is held in place (e.g. by pressing the distal end 1358 of the nose 1316of the distal housing 1310 against a patient's tissue), the proximalhousing 1308 may be moved distally relative to the distal housing 1310.The movement of the proximal housing 1308 may be transferred via thepower assembly 1306 (discussed in more detail below) to cause the powerassembly 1306 and syringe 1304 to slide distally from a retractedposition (shown in FIGS. 19A-19B) relative to the distal housing 1310 ifthe distal force on the proximal housing 1308 is above the necessaryforce threshold. The threshold force required may be due to the frictionbetween the outer surface of the syringe body 1602 and the inner surfaceof the syringe sleeve 1630. In some variations, the friction mayadditionally or alternatively be generated between the syringe body 1602and the inner surface of the syringe sleeve 1630 by a seal attached tothe inner surface of the syringe sleeve 1630. When the threshold distalforce is reached, the power assembly 1306 and syringe 1304 may be moveddistally toward the nose 1316 of the distal housing 1310, such that thesyringe 1304 may move toward an extended position (described above withrespect to syringe 104 of injection device 100), as shown in FIG. 19C.

As the distal tip 1624 of the needle 1606 approaches the distal opening1312 of the nose 1316, the shield of the needle safety assembly 1400 maybe unlocked from a retracted position, as described in detail above withrespect to injection device 100. As the distal tip 1624 of the needle1606 moves to extend beyond the distal end 1358 of the nose 1316, theneedle 1606 may pierce tissue pressed against the distal end 1358 of thenose 1316. The syringe 1304 may continue to move distally relative tothe syringe sleeve 1630 until the syringe 1304 has reached an extendedposition, as shown in FIG. 19D. At an extended position, the distal tip1624 of the needle 1606 may have reached the desired depth (describedabove). In some variations, when the syringe 1304 reaches an extendedposition, further distal movement relative to the distal housing 1310may be resisted by a proximal lip 1652 extending radially outward fromthe proximal end 1650 of the syringe body 1602, which may be configuredsuch that it may fit within the proximal portion 1634 of the syringesleeve 1630 but may not be able to enter the distal portion 1632 of thesyringe sleeve 1630. Once the syringe 1304 reaches an extended position,the canister manifold 1866 (described below) may also engage with thepressure chamber 1824 via flexures 1868 on the canister manifold 1866.

It should be noted that the power assembly 1306 and syringe 1304 maymove distally together with distal force on the proximal housing 1308,rather than the power assembly 1306 acting on the syringe 1304 (e.g., tocause the plunger 1710 to move distally within the syringe cavity 1604to act on the seal 1610 and displace the contents of the reservoir1614), due to the relative amounts of force required to move the powerassembly 1306 and syringe 1304 relative to the distal housing 1310, andto cause the plunger 1710 to move distally within the syringe cavity1604. More specifically, the amount of force required to overcome thefriction between the outer surface of the syringe body 1602 of thesyringe 1304 and the inner surface of the syringe sleeve 1630 may beless than the amount of force to cause the plunger 1710 to move distallywithin the syringe cavity 1604, described in detail below.

If the distal force on the proximal housing 1308 is released while thepower assembly 1306 and syringe 1304 are moving from a retractedposition to an extended position, the power assembly 1306 and syringe1304 may stay in place in an intermediate position relative to thesyringe sleeve 1630.

After the power assembly 1306 and syringe 1304 have moved distallyrelative to the distal housing 1310 such that the syringe 1304 is in anextended position and the distal tip 1624 of the needle 1606 is at thedesired depth, additional distal force on the proximal housing 1308 maybe transmitted into distal motion of the ram 1702 relative to thesyringe cavity 1604, if the force is above the necessary forcethreshold. When the force is above the necessary force threshold, theplunger 1710 and seal 1610 may begin to be moved distally relative toand within the syringe cavity 1604, as shown in FIG. 19E, which maydecrease the volume of the reservoir 1614 and displace the contents ofthe syringe cavity 1604 through the lumen 1608 of the needle 1606, asdescribed above with respect to injection device 100. The thresholdforce required to move the plunger 1710 and seal 1610 distally withinthe syringe cavity 1604 may be due, first, to a ridge 1670 extendingradially inward from the inner surface 1612 of the syringe cavity 1604.Before the seal 1610 has been moved within the syringe cavity 1604, theridge 1670 may be located distally to the seal 1610. When sufficientdistal force is applied to the proximal housing 1308 to deflect the seal1610 distally over the ridge 1670, the seal 1610 is then able to movefurther distally within the syringe cavity 1604, if the force issufficient to overcome friction between the seal 1610 and plunger 1710and the inner surface 1612 of the syringe body 1602, as well as betweenthe plunger 1710 and the syringe cap 1836. Additional force to move theplunger 1710 and seal 1610 distally relative to and within the syringecavity 1604 may also be due to the power assembly 1306, described below.

As described above with respect to the power assembly 106 of injectiondevice 100, the power assembly may provide an injection force sufficient(alone or in addition to injection force supplied by the user) to injecta given volume of a given formulation through a given size needle in agiven time, as described in detail with regard to power assembly 106.Like the power assembly 106, power assembly 1306 may comprise a storedenergy source and a rate control assembly. As in the power assembly 106described with respect to injection device 100, the power assembly 1306may comprise a stored energy source 1802, which may be configured toprovide force to displace of the contents of reservoir 1614 of thesyringe 1304 through the lumen 1608 of the needle 1606, and a ratecontrol assembly 1804, which may comprise a braking assembly that maylimit or restrict the stored energy source 1802 from contributing to thedisplacement of the contents of the reservoir 1614 of the syringe 1304through the lumen 1608 of the needle 1606. In the embodiment of theinjection device 1300 shown, the stored energy force 1802 may comprise acompressed gas or liquid propellant in a supercritical state. Thecompressed gas or liquid propellant may be held within container, suchas a canister 1806 (e.g., a double-crimped metal canister), which may belocated at the proximal end 1320 of the proximal housing 1308. Thecanister 1806 may be fixedly attached to the end cap 1318 of theproximal housing 1308, such that distal motion of the proximal housing1308 may cause distal motion of the canister 1806. In some variations,the canister 1806 may be attached to the end cap 1318 of the proximalhousing 1308 by a set of flexures extending distally from the inside ofthe end cap 1318 that may snap over the canister 1806 to retain it.

The compressed gas or liquid propellant may comprise any gas that issuitable for compression. In some variations, the compressed gas orliquid propellant may comprise a gas that is in a gaseous state at highpressures (e.g., N2, Ar, or compressed air). In these variations, whenthe compressed gas is released from the canister 1806, the outputpressure may decrease as the compressed gas leaves the canister 1806. Inother variations, the liquid propellant may comprise a gas that is asaturated liquid at high pressures (e.g., CO2 and R134A (also known asHF134A or HFC-R134a)). In these variations, when the liquid propellantis released from the canister 1806, the output pressure may be constant,as long as some propellant in liquid form remains in the canister 1806.The compressed gas or liquid propellant may have any suitable saturationpressure.

When the compressed gas or liquid propellant in a supercritical state isreleased from the canister 1806 through a valve 1808 (described below),it may cause the seal 1610 of the syringe 1304 to move distally relativeto and within the syringe cavity 1604, which may cause the contents ofthe reservoir 1614 to be displaced through the needle 1606 of thesyringe 1304. In some variations, the force from the compressed gas orliquid propellant may act directly on all or a portion of the proximalside of the seal. In other variations, the force from the compressed gasor liquid propellant may act indirectly on the seal; that is, the forcemay act on a surface other than the seal, which may in turn cause distalmovement of the seal. In yet other variations, the force from thecompressed gas or liquid propellant may act both directly and indirectlyon the seal. In each of these variations, the force from the compressedgas or liquid propellant may act on surface areas (i.e., the surfacearea orthogonal to the longitudinal axis) of varying sizes. In somevariations, the force may act on a surface having a cross-sectionalsurface area approximately equal to the cross-sectional surface area ofthe syringe cavity, for example, by acting directly on the seal. Inother variations, the force may act on a surface area smaller than thecross-sectional area of the syringe cavity, for example by acting on aportion of the seal or on an annular surface area radially outside thesyringe cavity having a smaller cross-sectional surface area than thesyringe cavity. In yet other variations, the force from the compressedgas or liquid propellant may act on a surface area larger than thecross-sectional surface area of the syringe cavity, for example byacting on the seal and on an annular surface area radially outside ofthe syringe cavity, or by acting on an annular surface area radiallyoutside of the syringe cavity having a larger cross-sectional surfacearea than the syringe cavity. One portion (e.g., a proximal portion) ofthe flow path may have the same or different cross-sectional (i.e.,orthogonal to the longitudinal axis) profile as a second portion (e.g.,a distal portion) of the flow path. In some variations, the flow path ofthe compressed gas or liquid propellant may be linear, while in othervariations, the flow path may be non-linear. For example, there may beno linear flow path between two locations in the flow path of thecompressed gas or liquid propellant (e.g., the proximal-most anddistal-most locations), or the flow path of the compressed gas or liquidpropellant may have two or more segments not parallel to each other.

In variations in which the force may act on a larger surface area, thismay allow the compressed gas or liquid propellant to generate morepressure to cause the seal to move distally. The saturation pressure ofthe compressed gas or liquid propellant, and the cross-sectional surfacearea of the upon which the pressure may act, may thus be chosen intandem to delivery an appropriate force based on the formulationviscosity, needle choice, injection volume, and desired injection time.In some variations, for example, the power assembly may be capable ofinjecting 1.9 mL of 39 cP solution through a 27 gauge needle in 10seconds by applying about 52-54N of force. For example, in somevariations, the injection device 1300 may use a liquid propellant with asaturation pressure of about 850 PSIa (e.g., CO2) acting on across-sectional surface area of about 0.014 square inches, which maysupply about 52N of force. In other variations, the injection device1300 may use a liquid propellant with a saturation pressure of about 85PSIa (e.g., R134A) acting on a cross-sectional surface area of about0.138 square inches. In other variations, the injection device 1300 mayuse a compressed gas with a typical pressure of about 2700 PSIa (e.g.,N2) acting on a cross-sectional surface area of about 0.0043 squareinches. In other variations, the injection device 1300 may use acompressed gas with a typical pressure of about 1750 PSIa (e.g., Ar)acting on a cross-sectional surface area of about 0.0067 square inches.It should be appreciated that these pressures, surface areas, and forcesare merely illustrative examples; any suitable combination may be chosento achieve a desired injection force.

As shown in FIGS. 19A-19G and illustrated with arrows in FIG. 20A, thestored energy source 1802 may comprise a flow-directing assembly fordirecting the compressed gas or liquid propellant when released. Theflow-directing assembly may direct the compressed gas or liquidpropellant distally through the inner lumen 1746 of the plunger 1710,radially outward through redirection openings, and into a pressurizationregion 1812 formed distally to a syringe cap 1836. More specifically, asdescribed above, the plunger of the ram 1702 may comprise an inner tube1742 located coaxially within an outer tube 1744. The inner tube 1772and outer tube 1744 may form an inner lumen 1746 within the inner tube1772, and an outer annular lumen 1748 between the inner tube 1772 andouter tube 1744. The proximal opening 1750 of the inner lumen 1746 maybe connected to the proximal opening 1814 of the valve 1808. The distalopening 1752 of the inner lumen 1746 may be in fluid communication withan inflow opening 1818 of a manifold 1816. The inflow opening 1818 ofthe manifold 1816 may be in fluid communication with one or more outflowopenings 1820 of the manifold 1816. In some variations, the manifold1816 may have four outflow openings 1820 connected to the inflow opening1818, and the outflow openings 1820 may be located away from thelongitudinal axis of the manifold 1816, such that the outflow openings1820 are directed outside of the syringe body 1602. The outflow openings1820 of the manifold 1816 may be in fluid communication with thepressurization region 1812.

As shown in FIG. 20A and in more detail in FIG. 20B, the pressurizationregion 1812 may be formed within a pressure chamber 1824, distally to asyringe cap 1836 and annularly to the syringe body 1602. The pressurechamber 1824 may comprise a cylinder 1826 having a lumen 1828 between aproximal end 1830 and a distal end 1832. The proximal end 1830 of thepressure chamber 1824 may be engaged with the canister manifold 1866 viaflexures 1868 when the syringe 1304 is in an extended position, asdescribed above. The distal end 1832 of the pressure chamber 1824 mayform a seal 1834 around the proximal portion 1634 of the syringe sleeve1630, such that the proximal portion 1634 of the syringe sleeve 1630 maybe located within the lumen 1828 of the pressure chamber 1824. Thesyringe sleeve 1630 may be slidable within the seal 1834. The syringecap 1836 may comprise a main body 1838, which may be slidably disposedwithin the pressure chamber 1824. The syringe cap 1836 may create a seal1840 with the inner surface of the cylinder 1826 of the pressure chamber1824 sufficient to resist pressurized gas travelling across the seal1840 between the syringe cap 1836 and the inner surface of the cylinder1826 of the pressure chamber 1824. The syringe cap 1836 may also have alumen 1842 therethrough, which may be configured to allow the plunger1710 of the ram 1702 to move therethrough. There may also be a seal 1844between the surface of the syringe cap 1836 forming the lumen 1842 andthe plunger 1710 sufficient to resist pressurized gas travelling acrossthe seal 1844 between the syringe cap 1836 and the plunger 1710.Extending distally from the main body 1838 of the syringe cap 1836 maybe one or more latches 1846. Each latch 1846 may comprise an elongateportion 1848 having a proximal portion attached to the main body 1838 ofthe syringe cap 1836, and a tab 1850 located at the distal end of theelongate portion 1848. The tab 1850 may be configured to fit into arecess, slot, or other indentation (e.g. recess 1674) in the proximalportion 1634 of the syringe sleeve 1630, described above. When thelatches 1846 are engaged with the syringe sleeve 1630, the position ofthe syringe cap 1838 may be fixed relative to the position of thesyringe sleeve 1630.

The seal 1834 between the pressure chamber 1824 and the proximal portion1634 of the syringe sleeve 1630, the seal 1840 between the syringe cap1836 and the pressure chamber 1824, and the seal 1844 between thesyringe cap 1836 and the plunger 1710 may thus create a variable-volumepressurization region 1812. The volume of the pressurization region 1812may be at a minimum when the proximal portion 1634 of the syringe sleeve1630 is adjacent to the distal end 1832 of the pressure chamber 1824, asshown in FIG. 20A. As the compressed gas or liquid propellant flows intothe pressurization region 1812, the pressure from the compressed gas orliquid propellant may urge the distal end 1832 of the pressure chamber1824 distally relative to the syringe sleeve 1630, in order to increasethe volume of the pressurization region 1812. The volume of thepressurization region 1812 may be at a maximum when the pressure chamber1824 has moved fully distally such that the distal end 1832 of thepressure chamber 1824 may be adjacent to the distal end 1314 of thedistal housing 1310, as shown in FIG. 19F.

As the pressure chamber 1824 is urged distally relative to the syringesleeve 1630, this may in turn urge the plunger 1710 distally relative tothe syringe cavity 1604. As the plunger 1710 slides distally relative toand within the syringe cavity 1604, this may in turn push the seal 1610distally relative to the syringe cavity 1604, which may in turn decreasethe volume of the reservoir 1614 of the syringe 1304. This may cause thecontents of the reservoir 1614 to be displaced through the lumen 1608 ofthe needle 1606 of the syringe 1304, as described above.

As shown with arrows in FIG. 20C, the injection device 1300 may furthercomprise a venting pathway for gas at atmospheric pressure into theregion 1682 of the syringe cavity 1604 proximal to the seal 1610. Thismay limit the development of negative pressure in the region 1682 as theseal 1610 moves distally relative to and within the syringe cavity 1604.Limiting the development of negative pressure in the region 1682 may bedesirable to avoid an unpleasant force profile experience for the useras the injection proceeds, and/or may be desirable to limit the riskthat any leakage from the pressurization region 1812 could cause directpressurization of the seal 1610, which in turn might increase the riskof leakage into the reservoir 1614, in those variations of the device inwhich direct pressurization of the seal 1610 is not intended. In somevariations, this venting pathway may be created by further ventingopenings in the manifold 1816. The manifold 1816 may comprise one ormore inflow venting openings 1862 in fluid communication with the region1682 of the syringe cavity 1604 proximal to the seal 1610, and one ormore outflow venting openings 1864 in fluid communication with ambientpressure within the housing 1302 via the outer annular lumen 1748 of theplunger 1710.

The distal movement of the plunger 1710 to press against the seal 1610of the syringe 1304, however, may at times be resisted or limited by therate control assembly 1804. In some variations, the rate controlassembly 1804 may comprise a valve 1808 and canister manifold 1866, asshown in FIGS. 19A-19G. When the valve 1808 is in a closedconfiguration, the valve 1808 may limit the ability of the compressedgas or liquid propellant to leave the canister 1806, and thus thecompressed gas or liquid propellant may not act upon the pressurechamber 1824 to move the pressure chamber 1824 distally, and thereforemay not provide force causing distal movement of the plunger 1710 andseal 1610 within the syringe cavity 1604 of the syringe 1304, asdescribed above. When the valve 1808 is in an open configuration, thecompressed gas or liquid propellant may be able to leave the canister1806 and act upon the pressure chamber 1824 distally, and may thereforeprovide force to distally move the plunger 1710 and the seal 1610 withinthe syringe cavity 1604 to displace the contents of the reservoir 1614through the lumen 1608 of the needle 1606. In some variations, the valve1808 may also have an intermediate configuration, wherein the valve 1808partially restricts the flow of the compressed gas or liquid propellant,but need not have such an intermediate configuration. The canistermanifold 1866 may create a seal between the valve 1808 and pressurechamber 1824. The canister manifold 1866 may comprise any suitablematerial, such as but not limited to a compliant material such asplastic with an overmold of thermoplastic elastomer.

In some variations, the valve 1808 may be biased toward the closedconfiguration. The valve 1808 may be moved into an open configuration byapplying distal force on the valve 1808 by the canister 1806. Thisdistal force may be applied by applying distal force to the proximalhousing 1308. When a distal force is applied to the proximal housing1308 while the distal housing 1310 is held in place (e.g. by pressingthe distal end 1358 of the nose 1316 of the distal housing 1310 againsta patient's tissue), the proximal housing 1308 and the canister 1806 maybe moved distally relative to the distal housing 1310, as well asrelative to the pressure chamber 1824 and canister manifold 1866. Thismay cause the valve 1808 to press against the canister manifold 1866,which may cause the valve 1808 to open. As a result, the valve 1808 mayopen, releasing the pressurized gas from the canister 1806 and throughthe valve 1808, the canister manifold 1866, the inner lumen 1746 of theplunger 1710, and the manifold 1816, and into the pressurization region1812, as described above. This may cause the volume of thepressurization region 1812 to increase, which may urge the plunger 1710and seal 1610 distally into the syringe cavity 1604 of the syringe 1304to displace the contents of the reservoir 1614 through the lumen 1608 ofthe needle 1606, as described above. FIG. 23 shows a graph ofillustrative forces for an injection device having a power assemblysimilar to the power assembly 1306 of the injection device 1300. Thegraph illustrates the amount of user force required to displacesimulated liquids having a range of viscosities with and without acanister installed in the injection device, with the seal displacing thecontents of the reservoir at a rate of approximately 6 mm/s. As can beseen, the force required with the canister installed is approximatelythe same for all three stimulated viscosities—about 15 to 18N of forcefrom the user, approximately the valve actuation force—whereassignificantly higher forces are required when the canister is notinstalled. Thus, the graph indicates the forces that can be generated bythe power assembly in order to achieve the required injection force. Itshould be noted that this graph is merely illustrative of the forces fora similar device, and is not meant to indicate that the injection device700 may or must conform to this representation.

If the distal force on the proximal housing 1308 is released, the biasof the valve 1808 toward the closed configuration may cause the valve1808 to close, stopping or reducing the inflow of pressurized gas intothe pressurization region 1812. When the inflow of pressurized gas intothe pressurization region 1812 is stopped, the existing pressure in thepressurization region 1812 may cause the pressure chamber 1824 tocontinue to move distally relative to the syringe sleeve 1630 until thepressure in the pressurization region 1812 drops to the same level asambient pressure. After this initial coasting period, the displacementof the contents of the reservoir 1614 through the needle 1606 may stop.This may allow the user to selectively and reversibly start and stop theinjection process. In some variations, the power assembly 1306 maycomprise a mechanism to stop the injection process without allow for acoasting period. In some such variations, such a mechanism maydepressurize the pressurization region 1812 when distal force on theproximal housing 1308 is released. For example, the seal between thevalve 1808 and the canister manifold 1866 may be configured to leak whenthe distal force on the proximal housing 1308 is released.

It should be appreciated that in some variations, the rate controlassembly 1804 may comprise different type of valve or additionalelements. For example, in variations of the injection device using acompressed gas or liquid propellant with high pressures, the valve maycomprise a puncture mechanism and/or a pressure regulator, but need not.A puncture mechanism, such as but not limited to a spring-loaded pinwith a grenade-pin type release mechanism, or a spring-loaded gascanister with a stationary pin, may release the higher pressure gas. Apressure regulator, such as but not limited to a diaphragm regulatorusing a spring to regulate force on a popper valve, may bring the gasdown to a safe and usable pressure.

In some variations, the injection device 1300 may comprise anautocomplete mechanism. In some variations, the autocomplete mechanismmay allow the valve 1808 to be locked in an open configuration. When thevalve is locked in an open configuration, force from the compressed gasor liquid propellant may cause the seal to be moved distally until theinjection is complete and the full contents of the reservoir have beendisplaced. In these variations, the injection device may furthercomprise a pressure relief port that may allow pressure to be releasedonce the full contents of the reservoir have been displaced, to preventpressure build-up after the completion of the injection.

In some variations, one or more of the elements of injection device 1300may optionally comprise clocking features to correctly orient theelements relative to each other, as described above with respect toinjection device 100.

Another embodiment of an injection device 2600 is shown in FIGS. 26 and27A-27H. FIG. 26 is a perspective view of injection device 2600, whileFIGS. 27A-27H illustrate longitudinal cross-sectional views of theembodiment of an injection device 2600 of FIG. 26 in various stagesduring use. As shown there, the injection device 2600 may comprise ahousing 2602, a syringe 2604, and a power assembly 2606. The housing2602 may be similar to the housing 102, described above with respect toinjection device 100, and may have the same components, configurations,and functions. In some variations, this may optionally comprise a cap,which may be similar to the cap 148 described above with respect toinjection device 100, and may have the same components and functions asdescribed above.

The syringe 2604 of the injection device 2600 may be similar to thesyringe 104 described above with respect to injection devices 100, andmay have the same components, positions, and functions as describedabove.

In general, the injection device 2600 may initially be in a state havinga needle safety assembly 2622 extending from the distal end of thehousing 2602, such that the syringe is fully contained within thehousing 2602 and needle safety assembly 2622, without any exposure ofthe needle 2628 of the syringe 2604, as shown in FIG. 27A. In variationscomprising a cap, the cap may be removed from the injection device 2600before use. The distal end of the injection device 2622 may then bepressed against a patient's tissue. Proximal force from the patient'stissue (e.g., by the user (the patient or another person) holding thehousing 2602 and pressing the injection device 2600 against the tissue)may overcome the needle safety assembly's bias toward an extendedposition, moving the needle safety assembly 2622 from an extended to aretracted position, as shown in FIG. 27B (partially retracted) and FIG.27C (fully retracted). Retraction of the needle safety assembly 2622 mayexpose the needle 2628 of the syringe 2604, allowing the needle 2628 topierce the patient's tissue. Retraction of the needle safety assembly2622 may release a locking mechanism comprising an interlock ring 2634,which prevents distal motion of a plunger 2614 within the syringe 2604before the needle safety assembly 2622 is retracted. Once the lockingmechanism is released, as shown in FIG. 27C, a user's application ofdistal force on the proximal housing may cause the plunger 2614 to movedistally to contact the seal 2612 of the syringe 2604, as shown in FIG.27D, and then may cause both the plunger 2614 and seal 2612 to movedistally within the syringe cavity 2616. This may in turn cause thecontents of the reservoir 2630 of the syringe 2604 to be delivered tothe patient via the needle 2628. During the injection process, theinjection force applied by the user may be amplified by a stored energysource, while still allowing the user to selectively start and stop theinjection process at will. A power spring 2652 may be configured topress the plunger 2614 distally within the syringe cavity 2616, but whenno force is applied by the user, the power spring 2652 may be preventedfrom acting on the plunger 2614 by friction generated by braking pad(s)2658. When a user applies force to the injection device, the force mayreduce or eliminate the friction generated by the braking pad(s) 2658,thus allowing the power spring 2652 to act on the plunger. Once theplunger 2614 and seal 2612 have been depressed such that the full ornearly full dose has been delivered to the patient, the dose mayautocomplete and/or an end-of-dose indicator may be activated. FIG. 27Fillustrates the device with the plunger 2614 and seal 2612 nearly in thefinal distal position within the syringe cavity, with the end-of-doseindicator 2618 in an activated configuration. FIG. 27G illustrates thedevice with plunger 2614 and seal 2612 in the final distal positionwithin the syringe cavity. After the dose is complete, if the injectiondevice 2600 is removed from the patient, the needle safety assembly 2622may return to the extended position as shown in FIG. 27H, where alocking ring 2668 may prevent the needle safety assembly 2622 fromre-retracting.

Thus, as illustrated in the explanation above, depending on the stage ofthe injection process, distal force on the proximal housing 2624 may betransmitted into different motions. In a first stage, distal force onthe proximal housing 2624 may be transmitted into distal motion ofinjection device 2600 relative to the needle safety assembly 2622, ifthe needle shroud 2620 of the needle safety assembly 2622 is held inplace (e.g., by pressing the distal end of the shroud 2620 against apatient's tissue). In a second stage, distal force on the proximalhousing 2624 may be transmitted into displacement of the contents of thereservoir 2630 of the syringe 2604 (e.g., a formulation comprising atherapeutic agent) through the lumen of the needle 2628.

In some variations, the ram 2610 may be configured such that theseeffects of distal force on the proximal housing 2624 may occur in theorder described above. That is, the ram 2610 may be configured such thatdistal force on the proximal housing 2624 may be transmitted first intodistal motion of injection device 2600 relative to the needle safetyassembly 2622, and then transmitted second into displacement of thecontents of the reservoir 2630 of the syringe 2604 (e.g., a formulationcomprising a therapeutic agent) through the lumen of the needle 2628.This may be desirable, for example, because it may allow the syringe2604 to move distally such that the needle 2628 may pierce a patient'stissue before the contents of the syringe cavity 2616 of the syringe2604 are displaced through the lumen of the needle 2628.

In some variations, the ordering of effects of distal force on theproximal housing 2624 may be due to different amounts of force that arerequired for each motion. For example, the ram 2610 may transmit distalforce on the proximal housing 2624 into distal motion of the rest of theinjection device 2600 relative to the needle safety assembly 2622 whenthe force on the proximal housing 2624 is above a first threshold (e.g.,above about 1N, above about 2N, above about 3N, above about 4N, aboveabout 5N, above about 6N, above about 7N, or higher); and the ram 2610may transmit distal force on the proximal housing 2624 into displacementof the contents of the reservoir 2630 of the syringe 2604 through theneedle 2628 when the force on the proximal housing 2624 is above ahigher second threshold (e.g., above about 5N, above about 10N, aboveabout 15N, above about 20N, above about 25N, or higher). It should beappreciated that in some other variations, the ram 2610 may transmitdistal force on the proximal housing 2624 into different motions indifferent orders and by different mechanisms. For example, in somevariations the effect of the distal force may be chosen by a mechanismfor manual selection by the user. In should also be appreciated that theram 2610 may have fewer or more motions into which it may transmitdistal force onto the proximal housing 2624.

As described briefly above, in some configurations application of distalforce on the proximal housing 2624 may cause distal motion of injectiondevice 2600 relative to the needle safety assembly 2622. In an initialconfiguration before use, as shown in FIG. 27A, if the shroud 2620 ofthe needle safety assembly 2622 is held in place (e.g., by pressing thedistal end of the shroud 2620 against a patient's tissue), the proximalhousing 2624, distal housing 2632, power assembly 2606 (discussed inmore detail below), and syringe 2604 may slide distally relative to theneedle safety assembly 2622. In effect, this may move the needle safetyassembly 2622 from an extended position (as shown in FIG. 27A), througha partially retracted position (as shown in FIG. 27B), and finally to afully retracted position (as shown in FIG. 27C), in which the distal endof the shroud 2620 is flush with the distal end of the distal housing2632. As the needle safety assembly 2622 retracts, the distal tip of theneedle 2628 may move beyond the distal end of the shroud 2620, and theneedle 2628 may pierce tissue pressed against the distal end of theshroud 2620. When the needle safety assembly 2622 is fully retracted,the distal tip of the needle 2628 may have reached the desired depth(described above), and further distal movement of the needle 2628 may beresisted by the distal end of the distal housing 2632 pressing againsttissue.

The force required to cause retraction of the needle safety assembly2622 may be determined by a biasing element that may bias the needlesafety assembly 2622 toward the extended position. For example, as shownin FIGS. 27A-27H, the biasing element may comprise a compression spring2662. The compression spring 2662 may have a proximal end fixed relativeto the housing 2602 and a distal end fixed relative to the needle safetyassembly 2622, therefore biasing the shroud 2620 distally relative tothe housing 2602. When the needle safety assembly 2622 is in an extendedposition, the compression spring 2662 may be in an extended position, asshown in FIG. 27A. As the needle safety assembly 2622 moves toward thefully retracted position, it may compress, as shown in FIGS. 27B-27C.The needle safety assembly 2622 may remain in the fully retractedposition throughout the injection, as shown in FIGS. 27D-27G, until theproximal force on the shroud 2620 is removed (e.g., the distal end ofthe injection device 2600 is removed from a patient's tissue), asdescribed in more detail below.

The beginning of the injection (e.g., via distal motion of a plunger2614 within the syringe cavity 2616) may be restricted by a lockingmechanism before the needle safety assembly 2622 is fully retracted. Insome variations, the locking mechanism may comprise an interlock ring2634. The ram housing 2636 may comprise one or more flexures 2638configured to restrict movement of the ram 2610 distally relative to thesyringe 2604. As shown in FIG. 30, the plunger 2614 (described in moredetail below) may comprise a notch 2640 at its distal end, which mayextend circumferentially around the middle of a widened region 2642 atthe distal end of the plunger 2614. A wedge-shaped portion of theflexure(s) 2638 of the ram housing 2636 may fit into the notch 2640 inan initial locked state, as shown in FIG. 27A. When the wedge-shapedportions of the flexure(s) 2638 are engaged with the notch 2640, theymay restrict distal movement of the ram 2610. In order for the ram 2610to move distally, the flexure(s) 2638 may be flexed outward. Interlockring 2634 may comprise a ring-like structure (shown isolated in FIG.29B) shaped and sized to fit around the ram housing 2636 and within theproximal housing 2624 and/or distal housing 2632. When the interlockring 2634 is in its locked position (as shown in FIG. 27A), it may belocated around the flexure(s) 2638 of the ram housing 2636, which may inturn act as a hoop to restrict outward flexion of the flexure(s) 2638.The flexure(s) 2638 may be allowed to flex outward by displacement ofthe interlock ring 2634 such that it is no longer located around theflexure 2628, and thus no longer restraining it. FIG. 27C shows such anunlocked configuration. As shown there, the flexure(s) 2638 may haveroom to flex outward when the interlock ring 2634 is in a proximal,unlocked position. While the embodiment of the injection device 2600comprises three flexures 2638, it should be appreciated that in othervariations the injection device 2600 may comprise fewer (e.g., one ortwo) or more (e.g., four, five, six, or more) flexures.

The release of the locking mechanism may be tied to the retraction ofthe needle safety assembly 2622. That is, the locking mechanism mayrestrict distal motion of the plunger 2614 (described in more detailbelow) until the needle safety assembly 2622 is fully retracted, andthus until the needle 2628 is at its desired depth. In some variations,retraction of the needle safety assembly 2622 may cause proximaldisplacement of the interlock ring 2634. For example, the needle safetyassembly 2622 may comprise a proximal portion configured to engage theinterlock ring 2634. In injection device 2600, the proximal portion ofthe needle safety assembly 2622 may comprise one or more arms 2644. Whenthe arm(s) 2644 are in the proximal position (i.e., when the needlesafety assembly 2622 is retracted), the arm 2644 may engage theinterlock ring 2634. In FIG. 27B, the proximal tip of arm 2644 can beseen about to engage the interlock ring 2634. In FIG. 27C, the proximaltip of the arm 2644 has pressed against the distal side of the interlockring 2634, moving it proximally relative to the ram housing 2636 andinto the unlocked configuration.

A perspective view of the needle safety assembly 2622 is shown in FIG.29A. While shown as having three arms 2644, it should be appreciatedthat the needle safety assembly 2622 may have fewer (e.g., zero, one, ortwo) arms, or more (e.g., four, fix, or six) arms. FIG. 28A shows acutaway perspective view of a distal end of the injection device 2600,showing the needle safety assembly 2622 in a first configuration withthe shroud 2620 in an initial extended position. FIG. 28B shows the sameview in a second configuration, with the shroud 2620 in a retractedposition. As can be seen in these figures, as the shroud 2620 moves fromthe extended position to the retracted position, the needle safetyassembly 2622 (including the arms 2644) moves proximally relative to thedistal housing 2632, such that it may contact the interlock ring 2634. Aperspective view of an interlock ring 2634 is shown in FIG. 29B. Asshown there, in some variations the interlock ring 2634 may comprise oneor more protrusions 2646 on the distal surface (e.g., as shown there,three protrusions), which may correspond to the arms 2644 on the needlesafety assembly 2622 and may be configured to be engaged by the arms2644.

After the needle safety assembly 2622 is retracted, and thus theinterlock ring 2634 is displaced into an unlocked configuration, asshown in FIG. 27C, additional distal force on the proximal housing 2624may be transmitted into the distal movement of the ram 2610. The ram2610 may comprise a rod 2648 and a plunger 2614. The rod 2648 may befixedly attached on its proximal end to the end cap 2650 of the proximalhousing 2624, and thus may transmit distal force on the proximal housing2624 into distal force on the ram 2610. The ram 2610 may furthercomprise a plunger 2614. All or a proximal portion of the plunger 2614may be hollow, and the distal end of the rod 2648 may extend through anopen proximal end of the hollow plunger 2614. The rod 2648 may beslidable within the proximal portion of the plunger 2614 within alimited range of motion. This range of motion may be defined by avariable gap between the end cap 2650 and the proximal end 2676 of theplunger 2614, which may allow the rod 2648 (which is fixedly attached tothe end cap 2650) to slide distally within the plunger 2614 until theinterior of the end cap 2650 (e.g., contacts a protruding tubular bossof the end cap) contacts the proximal end 2676 of the plunger 2614. Thisrange of motion may facilitate variable application of a braking force,as described in more detail below.

The plunger 2614 may be configured to be slidable within the syringecavity 2616 of the syringe 2604. The distal end of the plunger 2614 maybe configured to engage with the seal 2612 of the syringe 2604.Initially, distal force on the proximal housing 2624 may cause the ram2610 to move distally, causing the flexure 2638 of the ram housing 2636to be deflected radially outward, until the distal end of the plunger2614 of the ram 2610 contacts the seal 2612, as shown in FIG. 27D. Insome variations, the initial distance between the distal end of theplunger 2614 and the seal may be between about 1 mm and about 10 mm.Once the distal end of the plunger 2614 has contacted the seal 2612,additional distal force on the proximal housing 2624 may be transmitteddistal movement of the plunger 2614 within the syringe cavity 2616. Ifthe plunger 2614 is moved distally relative to and within the syringecavity 2616, the plunger 2614 may push the seal 2612 distally relativeto and within the syringe cavity 2616. This movement of the seal 2612may decrease the volume of the reservoir 2630 containing the formulationcomprising a therapeutic or diagnostic agent. Thus, distal motion of theplunger 2614, and in turn of the seal 2612, relative to and within thesyringe cavity 2616 may cause the contents of the reservoir 2630 to bedisplaced through the lumen of the needle 2628. When the force is abovea necessary force threshold, distal force on the proximal housing 2624may continue to cause the contents of the reservoir 2630 to be displacedthrough the lumen of the needle 2628 until the seal 2612 has traveled tothe distal end of the syringe cavity 2616, at which time the full dosageof the therapeutic or diagnostic agent may have been injected into thepatient, as described in more detail above with respect to injectiondevice 100.

In some variations, once the locking mechanism is unlocked (e.g., theinterlock ring 2634 is displaced), the threshold force required to movethe plunger 2614 and seal 2612 distally within the syringe cavity 2616may be governed by the power assembly 2606. As described above withrespect to the injection device 100, the power assembly 2606 maycomprise a stored energy source and a rate control assembly. The storedenergy source may be configured to provide force to displace thecontents of the reservoir 2630 of the syringe 2604 by contributing tothe distal motion of the plunger 2614 and seal 2612 within the syringecavity 2616. The rate control assembly may comprise a braking assemblythat may limit or restrict the stored energy source from contributing tothe displacement of the contents of the reservoir 2630 of the syringe2604.

In injection device 2600, the stored energy source may comprise a powerspring 2652 (e.g., a compression spring). The power spring 2652 may bedirectly or indirectly attached or in contact with a first surface fixedrelative to the syringe 2604 on one end, and may be directly orindirectly attached or in contact with a second surface fixed relativeto the plunger 2614 of the ram 2610 on the other end. Thus, the forcefrom the power spring 2652 on the first and second surfaces may bias thefirst and second surfaces away from each other, which may in turn biasthe plunger 2614 distally relative to the syringe cavity 2616. In thevariation shown in FIGS. 26 and 27A-27H, the power spring 2652 may belocated within a ram housing 2636 and around the plunger 2614 of the ram2610. The ram housing 2636 may be located proximally to the syringe 2604and fixed relative thereto. The power spring 2652 may be configured tofit within the syringe cavity 2616 when the power spring 2652 is in anextended configuration. A spring sleeve 2654 may be located between thepower spring 2652 and the plunger 2614 of the ram 2610. In the variationshown in FIGS. 27A-27H, the proximal end of the power spring 2652 may beattached or connected to a proximal lip 2656 of the ram housing 2636,while the distal end of the power spring 2652 may be attached orconnected to the proximal side of the widened distal portion 2642 of theplunger 2614.

The power spring 2652 may be made of any suitable material, such as butnot limited to music wire, stainless steel, and spring steel. The springrate of the power spring 2652 may be chosen to deliver an appropriateforce based on the formulation viscosity, needle choice, volume, anddesired injection time, as described above. In some variations, forexample, the power spring 2652 may be configured to deliver a force ofup to about 5N, about 10N, about 15N, about 20N, about 25N, about 30N,about 35N, about 40N, about 45N, about 50N, about 55N, about 60N, about65N, about 70N, about 75N, about 80N, about 85,or about 90N when thepower spring 2652 initially begins to expand.

As described above, the rate control assembly of the power assembly 2606may slow, limit, or restrict the stored energy source from providingforce to displace the contents of the reservoir 2630 of the syringe2604. In injection device 2600, the rate control assembly may comprise afriction-based braking assembly. The rate control assembly may have aclosed configuration where friction from the rate control assembly maycounteract or partially or fully oppose the force from the stored energysource. The rate control assembly may also have an open configuration,where there is not a friction force opposing the stored energy source,or where the friction force opposes the stored energy force but is lessthan is required to fully resist the stored energy source from acting onthe plunger 2614.

In the variation of FIG. 26, the braking assembly may comprise one ormore braking pad(s) 2658, which may be attached to the outer surface ofthe plunger 2614. The portion of the plunger 2614 comprising the brakingpad(s) 2658 may be hollow and flexible, such that the outward force fromwithin the plunger 2614 may flex the braking pad(s) 2658 radiallyoutward. For example, the braking pad(s) 2658 may be located on flexures2674 of the plunger 2614 that are configured to be flexed radiallyoutward. Flexures 2674 can be seen more clearly in FIG. 30, which showsa perspective view of the ram 2610. The braking pad(s) 2658 may compriseany suitable material configured to form a high-friction interface withthe spring sleeve 2654. For example, the braking pad(s) 2658 maycomprise an elastomer (e.g., rubber, thermoplastic elastomer), which mayform a high friction interface with a metal spring sleeve. If outwardforce from within the plunger 2614 presses the braking pad(s) 2658radially outward (e.g., by flexing the flexures 2674 outward) into thespring sleeve 2654, friction between the braking pad(s) 2658 and springsleeve 2654 may be created or increased. In some variations, the brakingassembly may comprise two braking pads 2658 (e.g., located on tworadially opposite flexures 2674 of the plunger 2614). However, in othervariations the braking assembly may comprise fewer (e.g., one) or more(e.g., three, four, five, six, or more) braking pads 2658, although itshould be appreciated that in some instances it may be desirable for theradial loads generated by the braking pads to be radially symmetric,such that unopposed radially loads are avoided.

As shown in FIGS. 27A-27H, in one variation the outward force on thebraking pad(s) 2658 may be achieved by a wedge-shaped stopper 2660. Thestopper 2660 may be located at the distal end of the rod 2648, which asdescribed above may be located slidably within the hollow proximalportion of the plunger 2614. The hollow proximal portion of the plunger2614 may have a corresponding conical or wedge-shaped interior shape,located near or adjacent to the baking pad(s) 2658. When the ratecontrol assembly is in a closed configuration, the stopper 2660 mayexert a proximal force relative to the plunger 2614. This proximal forcemay press the stopper 2660 proximally against the correspondingwedge-shaped interior of the plunger 2614, flexing the braking pad(s)2658 outward. When the braking pad(s) 2658 are located adjacent to thespring sleeve 2654, this may generate sufficient friction to oppose thestored energy source (i.e., the rate control assembly may be in a closedconfiguration). In contrast, when the stopper 2660 is not pressedproximally against the corresponding wedge-shaped interior of theplunger 2614, and thus the braking pad(s) 2658 are not flexed outward,the friction between the braking pad(s) 2658 and the spring sleeve 2654may be reduced or eliminated, such that the stored energy source (e.g.,the power spring 2652) may act on the plunger 2614 (i.e., the ratecontrol assembly may be in an open configuration).

In some variations, the stopper 2660 may be proximally biased relativeto the plunger 2614, such that the stopper 2660 is biased toward aconfiguration in which it presses proximally against the interiorsurface of the plunger 2614, such that the rate control assembly is in aclosed configuration. This proximal bias may be generated by a biasingelement configured to bias the end cap 2650 of the proximal housing 2624and the plunger 2614 away from each other. As described above, the rod2648 may be fixedly attached on its proximal end to the end cap 2650 ofthe proximal housing 2624, while the distal end of the rod 2648 mayextend through an open proximal end of the hollow plunger 2614 such thatthe rod 2648 is slidable within the plunger 2614 within a limited rangeof motion. As shown in FIGS. 27A-27H, in one variation the biasingelement may comprise a compression spring 2664 having a proximal endfixed relative to the rod 2648 (e.g., attached to the interior surfaceof the end cap 2650 at a distal end) and a distal end fixed relative tothe ram 2610. When distal force is not being applied to the proximalhousing 2624, the stopper 2660 may thus be naturally biased proximallyagainst the interior of the plunger 2614, pressing the braking pad(s)2658 outwards. In contrast, when sufficient distal force is applied tothe proximal housing 2624 to overcome the biasing element, the stopper2660 may not press against the interior of the plunger 2614, and thusthe braking pad(s) 2658 may not be pressed outwards, such that the ratecontrol assembly is in an open configuration.

When the braking pad(s) 2658 are located adjacent to a surface withwhich they are configured to form a high-friction interface (e.g., thespring sleeve 2654), outward flexion of the braking pad(s) 2658 towardthe adjacent surface may generate friction. This friction may besufficient to oppose the stored energy source (e.g., the power spring2652), such that the plunger 2614 and seal 2612 are not moved distallywithin the syringe cavity 2616, and the injection does not proceed. Incontrast, when the braking pad(s) 2658 are located adjacent to a surfacewith which they are configured to form a high-friction interface (e.g.,the spring sleeve 2654) but the braking pad(s) 2658 are not flexedoutwards, there may be no friction force, or the friction force may below enough, that the stored energy source (e.g., the power spring 2652)can act on the plunger 2614 to move the plunger 2614 and seal 2612distally within the syringe cavity 2616, causing the injection toproceed.

In some variations, the friction force generated at the high-frictioninterface (e.g., between the braking pad(s) 2658 and the spring sleeve2654) may be at least 2 times the force generated by the biasing element(e.g., by compression spring 2664). In some variations, the frictionforce generated at the high-friction interface may be at least 3 timesthe force generated by the biasing element. In some variations, thefriction force generated at the high-friction interface may be at least5 times the force generated by the biasing element. In some variations,the friction force generated at the high-friction interface may be atleast 10 times the force generated by the biasing element. Accordingly,in these variations, the braking pad(s) may be able to resist motion ofthe plunger when the power spring is 2, 3, 5, or 10 times more powerfulthan the biasing element. For example, in one variation, the powerspring 2652 may apply an initial force in a compressed configuration ofapproximately 15N, while the biasing element may comprise a compressionspring 2664 configured to apply a force of about 7N-8N.

As shown in FIGS. 27A-27C, before the plunger 2614 and seal 2612 haveadvanced within the syringe cavity 2616, the braking pad(s) 2658 may belocated proximal to the proximal end of the spring sleeve 2654. In thisposition, the braking pad(s) 2658 may not be adjacent to anothersurface, and thus, may not generate any friction. As such, after theinterlock ring 2634 is displaced to allow distal motion of the plunger2614, the power spring 2652 may initially act unopposed on the plunger2614, moving the plunger 2614 distally until the braking pad(s) 2658enter the spring sleeve 2654. In some variations, this may allow theinitial space between the plunger 2614 and the seal 2612 to be quicklyclosed by distal motion of the plunger 2614. It may also in somevariations be desirable that the braking pad(s) 2658 not be locatedadjacent to the spring sleeve 2654 or another surface in an initialstate, so as to avoid the braking pad(s) experiencing a compression-set.The braking pad(s) 2658 may thus enter the spring sleeve 2654immediately after initiation of the injection.

Additional distal force applied to the proximal housing 2624 may causethe plunger 2614 and seal 2612 to advance distally within the syringecavity 2616, beginning to force the contents of the reservoir 2630 outthrough the lumen of the needle 2628. As the plunger 2614 and seal 2612move distally, as shown in FIG. 27E, the braking pad(s) 2658 mayaccordingly move distally relative to the spring sleeve 2654. When nodistal force is applied to the proximal housing 2624 (or when the distalforce is below the threshold), the proximal bias on the stopper 2660 maybe sufficient to oppose the power spring 2652, causing the injection tostop. When instead sufficient distal force is applied to the proximalhousing 2624 to overcome the proximal bias on the stopper 2660, the ratecontrol assembly may be in an open configuration (e.g., the brakingpad(s) 2658 may not be pressed radially outward by the stopper 2660),and the power spring 2652 may apply force to push the plunger 2614 andseal 2612 distally within the reservoir 2630 of the syringe 2604. Asshown in FIG. 27E, the power spring 2652 may press against the proximalside of the widened region 2642 at the distal end of the plunger 2614.As the power spring 2652 expands during injection, the power spring 2652may extend into the syringe cavity 2616.

After the plunger 2614 and seal 2612 have begun to advance within thesyringe cavity 2616, the braking pad(s) 2658 may move distally to aposition adjacent the interior surface of the spring sleeve 2654, asshown in FIG. 27E. As such, the rate control assembly may be reversiblyand selectively moved between open and closed configurations byapplication of distal force to the proximal housing 2624. When distalforce is applied to the proximal housing 2624 while the distal end ofthe injection device 2600 is held in place (e.g., by pressing the distalend of the injection device 2600 against a patient's tissue) the ratecontrol assembly may be moved to an open configuration. Morespecifically, the distal force may overcome the bias of the compressionspring 2664. As a result, the rod 2648 and stopper 2660 may be moveddistally relative to the plunger 2614, which may in turn remove outwardpressure on the braking pad(s) 2658 and reduced the friction between thebraking pad(s) 2658 and the spring sleeve 2654. This may in turn allowthe power spring 2652 to act on the plunger 2614 to urge the seal 2612distally to displace the contents of the reservoir 2630 through thelumen of the needle 2628. If the distal force on the proximal housing2624 is released, the bias of the rate control assembly toward a closedconfiguration may cause the injection to stop. When distal force isreleased, the biasing force on the ram 2610 and stopper 2660 may causethem to move proximally relative to the plunger 2614, applying anoutward force on the braking pad(s) 2658. As a result, friction betweenthe braking pad(s) 2658 and the spring sleeve 2654 may resist the forceof the stored energy source.

It should be appreciated that in this configuration, the force appliedto the proximal housing 2624 is also applied to the plunger 2614. Thatis, the total force moving the seal 2612 distally within the syringecavity 2616 includes both a user's force and the force generated by thestored energy source (e.g., the power spring 2652). This may allow theuser to increase the speed of the injection process beyond the maximumspeed generated by the stored energy source alone. Similarly, the usermay be able to slow the speed of the injection process by applyingsufficient distal force to partially but not fully open the rate controlassembly (e.g., to decrease but not eliminate the friction between thebraking pad(s) 2658 and the spring sleeve 2654). As such, the user maybe able to selectively and reversibly start and stop, or increase ordecrease the speed of, the injection process. FIG. 31 shows anillustrative graph of the user force required to perform an injectionusing an injection device having a power assembly similar to the powerassembly 2606 of the injection device 2600. As shown, in one variation,the user force required is approximately 10 N with the power assembly(indicated as “Assisted”), while without the power assembly (indicatedas “Baseline”), the user force required is approximately 23 N. Thus, thedevice may have a force multiplication factor of about 2.3. It should benoted that this graph is merely illustrative of the user force requiredfor a similar device, and is not meant to indicate that the injectiondevice 2600 may or must conform to this representation.

In some variations the injection device 2600 may comprise anautocomplete mechanism, which may cause the full volume of the reservoir2630 to be automatically displaced through the lumen of the needle 2628within a certain tolerance of the total injection (e.g., within about85% of the injection, within about 90% of the injection, within about95% of the injection, or more, or within about 1 mm of fulldisplacement, about 2 mm of full displacement, about 3 mm of fulldisplacement, or about 4 mm of full displacement, etc.), regardless of auser's application of distal force to the proximal housing 2624. In somevariations, autocompletion may be caused by the braking pad(s) 2658 nolonger contacting the spring sleeve 2654. For example, when the seal2612 is near the distal end of the syringe cavity 2616, the plunger 2614may have travelled distally within the syringe cavity 2616 such that thebraking pad(s) 2658 may reach the distal end of the spring sleeve 2654.When the braking pad(s) 2658 move distally beyond the spring sleeve2654, they may no longer be in contact with the spring sleeve 2654.Accordingly, there may be no friction between the braking pad(s) 2658and the spring sleeve 2654, and thus no force opposing the distal forcefrom the power spring 2652. As a result, the dose may autocomplete dueto distal force on the plunger 2614 from the power spring 2652.

Injection device 2600 may also comprise an indicator that, like theindicators described with respect to the injection device 100, mayindicate the progress or completion of the injection, and may haveactivated and inactivated configurations. In some variations of theinjection device 2600, the indicator may comprise an end-of-doseindicator 2618 to alert the user that the full dose has been displacedfrom the reservoir 2630 of the syringe 2604, and/or that the seal 2612has traveled the full length of the reservoir 2630 to the distal end ofthe syringe cavity 2616. Additionally or alternatively, the end-of-doseindicator 2618 may alert the user that nearly (e.g., greater or equal toabout 85%, greater or equal to about 90%, greater or equal to about 95%,or more) the full dose has been displaced and/or that the seal 2612 hastraveled nearly (e.g., greater or equal to about 85%, greater or equalto about 90%, greater or equal to about 95%, or more, or within about 1mm of full displacement, about 2 mm of full displacement, about 3 mm offull displacement, or about 4 mm of full displacement, etc.) the fulllength of the reservoir 2630 to the distal end of the syringe cavity2616. In variations in which the injection device has both anautocomplete mechanism and an end-of-dose indicator, these may betriggered at the same time. If the end-of-dose indicator is deployedbefore the dose has been fully delivered, this may reduce the likelihoodthat a user fails to deliver the full dose.

The end-of-dose indicator 2618 may have different visual appearancesassociated with the inactivated and activated configurations. FIGS.27A-27E show the end-of-dose indicator 2618 in the inactivatedconfiguration, while FIGS. 27F-27H show the end-of-dose indicator 2618in an activated configuration. The end-of-dose indicator 2618 may beseen through the housing in the activated configuration, while not seenthrough the housing in the inactivated configuration.

In the variation shown in FIGS. 27A-27H, the end cap 2650 of theproximal housing 2624 may be configured such that when the end-of-doseindicator 2618 is adjacent to the inner surface of the end cap 2650, atleast a portion of the end-of-dose indicator 2618 may be seen fromoutside the end cap 2650 through a viewing portion. In some variations,at least a portion of the end-of-dose indicator 2618 may have a color orpigment that may be capable of being more easily noticed, such as butnot limited to red, yellow, orange, green, magenta, blue, and the like.In order for the end-of-dose indicator 2618 to be seen through at leasta portion of end cap 2650, in some variations, at least a portion of theend cap 2650 may be translucent. In variations in which a portion of theend cap 2650 is translucent, the level of translucency may be such thatthe coloring of the end-of-dose indicator 2618 may be perceived throughthe end cap 2650 only when the end-of-dose indicator 2618 is adjacent ornearly adjacent to the viewing portion. In other variations, the end cap2650 may comprise a transparent or open region configured such that noportion of the end-of-dose indicator is visible in the inactivateconfiguration, and the end-of-dose indicator 2618 is only visiblethrough the viewing portion when the end-of-dose indicator 2618 isadjacent to the transparent or open region, for example, because of theviewing angle. For instance, in some such variations, the viewingportion may comprise a transparent region around the circumference ofthe end cap 2650, and the end-of-dose indicator 2618 may only be visiblethrough the viewing portion when aligned adjacent to the viewingportion. The end-of-dose indicator 2618 may comprise a lumentherethrough, such that the end-of-dose indicator 2618 fits within theproximal housing 2624 and around the ram housing 2636.

A biasing element may be configured to bias the end-of-dose indicator2618 toward an activated configuration. The biasing element may have acompressed configuration and an expanded configuration. The biasingelement may be in a compressed configuration when the end-of-doseindicator 2618 is in an inactivated configuration, and the biasingelement may be in an expanded configuration when the end-of-doseindicator 2618 is in an activated configuration. In some variations, thebiasing element may comprise a compression spring 2666. The proximal endof the compression spring 2666 may be connected to or in contact withthe end-of-dose indicator 2618, and the distal end of the compressionspring 2666 may be connected to or in contact with an object distal tothe end-of-dose indicator 2618, such as the interlock ring 2634(described above). The biasing element may thus bias the end-of-doseindicator 2618 toward the proximal end of the proximal housing 2624.

As shown in FIGS. 27A-27E, the ram housing 2636 may comprise one or morelatch(es) 2670, which may hold the end-of-dose indicator 2618 in aninactivated configuration until released. The latch(es) 2670 may eachcomprise a radially outward-extending lip that may press distallyagainst the proximal surface of the end-of-dose indicator 2618. This lipmay resist the biasing force from the biasing element (e.g., compressionspring 2666) tending to push the end-of-dose indicator 2618 toward anactivated configuration. When the end-of-dose indicator 2618 is releasedfrom the latch(es) 2670, the indicator may no longer be held in aninactivated configuration. The end-of-dose indicator 2618 may bereleased by radially inward force on the latch(es) 2670. In thevariation shown in FIGS. 27A-27H, the radially inward force may beapplied by a portion of the end cap 2650. As shown in FIG. 27E, the endcap 2650 may comprise a rim 2672 extending distally from the interior ofthe end cap 2650, which may in some variations have a cup shape asshown. As end cap 2650 moves distally relative to the latch(es) 2670 andram housing 2636 during the injection, the rim 2672 may come intocontact with an angled portion of the latch(es) 2670, as shown in FIG.27F. This may generate a radially inward force on the latch(es) 2670.The latch(es) 2670 may thus be flexed inwardly, releasing the radiallyoutward-extending lip from the proximal surface of the end-of-doseindicator 2618. The ram housing 2636 may comprise any suitable number oflatches 2670, such as but not limited to one, two, three, four, five,six, or more. The rim 2672 may have any suitable correspondingconfiguration, such as but not limited to a continuous cup shape, orindividual arms each configured to contact a latch 2670. Once released,the biasing force from the compression spring 2666 may cause theend-of-dose indicator 2618 to move proximally toward an activatedconfiguration, as shown in FIGS. 27F-27H. In some variations, theend-of-dose indicator 2618 may be configured to produce a sudden,audible, and/or tactile indication of having delivered the full ornearly full dose.

After completion of the injection, the injection device 2600 may beremoved from the patient. When proximal force from the tissue on theshroud 2620 of the needle safety assembly 2622 is removed, a biasingelement (e.g., the compression spring 2662) may cause the needle shroud2620 to return to an extended configuration. In some variations, theshroud 2620 of the needle safety assembly 2622 may additionally oralternatively be configured to be locked in an extended configurationafter moving from a retracted configuration to an extendedconfiguration. This feature may limit the ability of a needle 2628 toextend from the distal end of the nose to pierce or otherwise contacttissue or other surfaces after the injection device 2600 has beenremoved from a patient's tissue. This may make the injection device 2600safer for the user and/or patient by limiting accidental needlesticks.It should be appreciated that in some variations, the needle safetyassembly 2622 may enter the locked extended configuration if theinjection 2600 is removed from the patient before the injection hasfully completed.

FIGS. 28A-28C show one variation of a mechanism by which the needlesafety assembly 2622 may be able to be initially retracted by proximalforce on the shroud 2620, but after having been retracted, re-extensionof the needle safety assembly 2622 may cause it to lock into theextended position. The needle safety assembly 2622 may comprise a shroudlocking ring 2668, shown isolated in FIG. 29C. The shroud locking ring2668 may sit between the proximal portion of the needle safety assembly2622 and distal housing 2632. The shroud locking ring 2668 may bemovable between three configurations: a first, stable configuration whenthe needle safety assembly 2622 is initially extended; a second,unstable configuration when the needle safety assembly 2622 isretracted; and a third, stable configuration when the needle safetyassembly 2622 is extended after having been retracted. The initialstable configuration is shown in FIG. 28A. As the needle safety assembly2622 moves toward a retracted configuration as shown in FIG. 28B,proximal movement of the proximal end of the needle safety assembly 2622may cause the shroud locking ring 2668 to rotate into the second,unstable configuration. As the needle safety assembly 2622 moves backtoward a retracted configuration as shown in FIG. 28C, the distalmovement of the proximal end of the needle safety assembly 2622 maycause the shroud locking ring 2668 to rotate into the third, stableconfiguration. Once the shroud locking ring 2668 has entered the third,stable configuration, it may block distal movement of the needle safetyassembly 2622.

More specifically, when the needle safety assembly 2622 is initially inthe extended position, the shroud locking ring 2668 may sit in a first,stable configuration against an internal shoulder of the distal housing2632, and may be biased proximally toward the internal shoulder bycompression spring 2662. The shroud locking ring 2668 and internalshoulder of the distal housing 2632 may comprise ramped surfaces, suchthat the shroud locking ring 2668 can sit against the internal shoulderin two different stable positions. When the needle safety assembly 2622retracts, a ramped surface 2680 on each arm 2644 of the needle safetyassembly 2622 may move into contact with a tab 2684 of the shroudlocking ring 2668. As the needle safety assembly 2622 and arm 2644 moveproximally, this may exert force on the tab 2684 that may cause theshroud locking ring 2668 to rotate (e.g., by between about 10 degreesand about 30 degrees, by about 15 degrees, or any suitable range).During this motion, the shroud locking ring 2668 may move distallyrelative to the internal shoulder of the distal housing 2632, allowingthe shroud locking ring 2668 to rotate over a peak formed by the rampedsurfaces of the internal shoulder. After the shroud locking ring 2668rotates over the peak, the compression spring 2662 may bias the shroudlocking ring 2682 back against the internal shoulder of the distalhousing 2632. Once the needle safety assembly 2622 is in a fullyretracted position, steps 2686 on the needle safety assembly 2622 mayinterface with tabs 2684 to prevent further rotation of the shroudlocking ring 2668. When the needle safety assembly 2622 moves backtoward a retracted configuration after having been in the retractedposition, the needle safety assembly 2622 may disengage from the shroudlocking ring 2682, and the shroud locking ring 2682 may further rotateunder the bias from compression spring 2662 until it reaches the second,stable configuration against the internal shoulder of the distal housing2632. In this configuration, further rotation of the shroud locking ring2668 may be resisted by tabs 2688 on the needle safety assembly 2622,but preventing further retraction of the needle safety assembly 2622.

While the variation of the injection device described immediately aboveis configured to lock in the extended configuration after having been ina retracted configuration, it should be appreciated that in othervariations, the needle shroud may not be configured to lock whenre-entering an extended position (e.g., in some variations, the needleshroud may continue to be able to be retracted from an extended positionin response to distal force).

In some variations, one or more of the elements of injection device 2600may optionally comprise clocking features to correctly orient theelements relative to each other, as described above with respect toinjection device 100.

While embodiments have been described and presented herein, thoseembodiments are provided by way of example only. Variations, changes,and substitutions may be made without departing from the embodimentsprovided by way of example. It should be noted that various alternativesto the exemplary embodiments described herein may be employed.

1. A device for injecting an agent, comprising: a syringe comprising asyringe cavity, a plunger element slidably received in the syringecavity, and a hollow needle in fluid communication with the syringecavity, wherein the plunger element is configured to move from aproximal position to a distal position; a power assembly configured totransmit force to the plunger element; and a user-actuated brakeassembly that is configured to reversibly resist movement of the plungerelement in at least one intermediate position between the proximalposition and the distal position.
 2. The device of claim 1, wherein thebrake assembly is biased to resist movement of the plunger element whenin an inactivated state, and permits movement of the plunger elementwhen in an activated state.
 3. The device of claim 2, wherein the brakeassembly is biased by a brake spring to resist movement of the plungerelement.
 4. The device of claim 1, wherein the power assembly comprisesa mechanical spring.
 5. The device of claim 1, wherein the plungerelement is further configured to simultaneously receive user-appliedforce that moves the plunger element toward the distal position.
 6. Thedevice of claim 1, further comprising a housing wherein the syringe islocated in the housing.
 7. The device of claim 6, wherein the housing iscoupled to the plunger element.
 8. The device of claim 7, wherein thehousing is configured to transmit user-applied force to the plungerelement.
 9. The device of claim 1, wherein the brake assembly comprisesa flexible, elongate brake cord.
 10. The device of claim 9, wherein thebrake cord provides a releasable friction fit to reversibly resistmovement of the plunger element.
 11. The device of claim 10, wherein thereleasable friction fit is provided by releasable tension in the brakecord.
 12. The device of claim 1, wherein the brake assembly comprises arigid friction element.
 13. The device of claim 1, wherein the brakeassembly acts on an outer surface of the syringe to reversibly resistmovement of the plunger element.
 14. The device of claim 1, wherein thebrake assembly acts on a surface fixed relative to the syringe toreversibly resist movement of the plunger element.
 15. The device ofclaim 1, wherein the brake assembly comprises an opening in which thesyringe resides.
 16. The device of claim 1, wherein the power assemblyis configured to pull the plunger element toward the distal position.17. The device of claim 1, wherein the power assembly is configured topush the plunger element toward the distal position.
 18. The device ofclaim 16, wherein the power assembly is further configured to push andpull the plunger element toward the distal position.
 19. The device ofclaim 6, wherein the syringe is slidably located in the housing and thesyringe is configured to move from a retracted position where a distaltip of the needle lies within the housing, toward an extended positionwhere the distal tip of the needle extends distal to the housing. 20.The device of claim 1, further comprising an extendable needle shroud,wherein the needle shroud is configured with a releasably locked,retracted state relative to the syringe, and an unlocked state thatpermits movement toward an extended position relative to the syringe.21. The device of claim 19, further comprising an extendable needleshroud, wherein the needle shroud is configured with a releasablylocked, retracted state relative to the syringe, and an unlocked statethat permits movement toward an extended position relative to thesyringe, and wherein the needle shroud is further configured to changeto the unlocked state before the distal tip of the needle extends distalto the housing.
 22. The device of claim 21, wherein the needle shroud isfurther configured to relock when the needle shroud reaches the extendedstate. 23-81. (canceled)
 82. A device for injecting an agent,comprising: a housing having a longitudinal axis; a syringe containingthe agent within a syringe cavity, wherein the syringe is located withinthe housing; a plunger slidable within the syringe, configured to bemoveable between a proximal position and a distal position, whereinmoving the plunger toward the distal position displaces the agent fromthe syringe; and a spring in contact with the plunger configured to biasthe plunger toward the distal position, wherein the plunger comprises abraking pad configured to be reversibly moveable between a firstconfiguration and a second configuration, wherein the braking padgenerates friction to resist movement of the plunger in the secondconfiguration.
 83. The device of claim 82, wherein the braking pad isconfigured to be moveable from the first configuration to the secondconfiguration by radially outward movement.
 84. The device claim 82,further comprising a stopper located within the plunger and movablebetween a proximal position and a distal position within the plunger,wherein the stopper is configured such that moving the stopper from thedistal position to the proximal position moves the braking pad from thefirst configuration to the second configuration.
 85. The device of claim84, wherein the stopper is biased toward the proximal position.
 86. Thedevice of claim 84, wherein the stopper is configured to be moveablebetween the proximal position and distal position by application ofdistal force on the housing.
 87. The device of claim 82, furthercomprising a retractable needle shroud configured to be moveable betweena retracted position and an extended position.
 88. The device of claim82, further comprising an end-of-dose indicator moveable between aninactivated and an activated configuration.
 89. (canceled)
 90. Thedevice of claim 1, further comprising an extendable needle shroud,wherein the needle shroud is configured with an unlocked extended statethat permits movement toward a retracted position relative to thesyringe and a locked extended state.
 91. The device of claim 90, whereinthe needle shroud is configured to enter the locked extended state whenthe needle shroud extends from a retracted state.